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Fecci, Peter Edward

Positions:

Assistant Professor of Neurosurgery

Neurosurgery
School of Medicine

Assistant Professor in Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2007

M.D. — Duke University School of Medicine

Ph.D. 2007

Ph.D. — Duke University

Internship, General Surgery

Massachusetts General Hospital

Residency, Neurosurgery

Massachusetts General Hospital

Postdoctoral Fellow

Dana Farber Cancer Institute

Instructor, Neurosurgery

Massachusetts General Hospital

News:

Grants:

Medical Scientist Training Program

Administered By
School of Medicine
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 1997
End Date
June 30, 2022

A Novel Clinical Challenge in Brain Tumor Immunology: T cell Sequestration

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
December 15, 2016
End Date
November 30, 2021

Laser Ablation using Robotic Neuroblate System (LAANTERN)

Administered By
Neurosurgery
AwardedBy
Monteris Medical, Inc.
Role
Principal Investigator
Start Date
March 01, 2016
End Date
December 31, 2020

Lost and Found: The Bone Marrow as Counterproductive Site of T cell Sequestration in GBM

Administered By
Neurosurgery
AwardedBy
Sontag Foundation
Role
Principal Investigator
Start Date
October 01, 2015
End Date
September 30, 2019

LITT and Short Course Radiation for Patients with GBM Requiring Standard Treatment Alternatives (LASR)

Administered By
Duke Cancer Institute
AwardedBy
Monteris Medical, Inc.
Role
Principal Investigator
Start Date
April 27, 2017
End Date
April 26, 2019

Directed Chemotherapy Delivery for Leptomeningeal Metastases

Administered By
Neurosurgery
AwardedBy
Minnetronix, Inc
Role
Co Investigator
Start Date
September 01, 2016
End Date
August 31, 2017
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Publications:

Biopsy of enlarging lesions after stereotactic radiosurgery for brain metastases frequently reveals radiation necrosis.

Stereotactic radiosurgery (SRS) offers excellent local control for brain metastases (BM) with low rates of toxicity. Radiation necrosis (RN) may occur after treatment and is challenging to distinguish from local recurrence (LR). We evaluated enlarging brain lesions following SRS that were subsequently biopsied to differentiate RN versus LR.This study reviewed patients receiving SRS for BM between 2008 and 2012 who underwent a biopsy for suspicion of RN versus LR on MRI. Data collection included demographics, radiation parameters, imaging findings, and post-biopsy pathology. Kaplan-Meier methods determined overall survival. Fisher's exact test assessed for association between lesion biopsy result and variables of interest.Thirty-four patients with 35 biopsied BM were included. Lesions were biopsied a median of 8.8 months after SRS. Most patients had primary lung cancer (11; 31.4%). Eleven (31.4%) biopsies were positive for LR and 24 (68.6%) showed RN only. Median overall survival was longer for patients with RN (31.0 mo) than for patients with LR (14.5 mo; P = 0.135). Time from SRS to biopsy was significantly different between RN and LR groups; 10 lesions (52.5%) biopsied ≤9 months after SRS showed LR, whereas 1 lesion (6.3%) biopsied >9 months after SRS showed LR (P = 0.004). For 16 (65.7%) lesions, management was changed or directed by the biopsy results.Stereotactic biopsy for accessible enlarging lesions after SRS appears diagnostically valuable in patients with few lesions and changes clinical management. RN should be suspected in patients with an enlarging lesion more than 9 months post-SRS.

Authors
Narloch, JL; Farber, SH; Sammons, S; McSherry, F; Herndon, JE; Hoang, JK; Yin, F-F; Sampson, JH; Fecci, PE; Blackwell, KL; Kirkpatrick, JP; Kim, GJ
MLA Citation
Narloch, JL, Farber, SH, Sammons, S, McSherry, F, Herndon, JE, Hoang, JK, Yin, F-F, Sampson, JH, Fecci, PE, Blackwell, KL, Kirkpatrick, JP, and Kim, GJ. "Biopsy of enlarging lesions after stereotactic radiosurgery for brain metastases frequently reveals radiation necrosis." Neuro-oncology 19.10 (October 2017): 1391-1397.
PMID
28472527
Source
epmc
Published In
Neuro-Oncology
Volume
19
Issue
10
Publish Date
2017
Start Page
1391
End Page
1397
DOI
10.1093/neuonc/nox090

Prospect of rindopepimut in the treatment of glioblastoma.

Rindopepimut (CDX-110) is a peptide vaccine that targets epidermal growth factor receptor variant III (EGFRvIII), a tumor-specific epitope expressed in the most common and lethal primary malignant neoplasm of the brain - glioblastoma (GBM). Areas covered: The EGFRvIII mutation introduces an 801 base pair in-frame deletion of the extracellular domain of the transmembrane tyrosine kinase, resulting in constitutive kinase activity, amplification of cell growth, and inhibition of apoptosis. Rindopepimut contains a 14mer amino acid peptide spanning the EGFRvIII mutation site that is conjugated to keyhole limpet hemocyanin (KLH). The EGFRvIII neoantigen is exclusively present on GBM cells, providing rindopepimut tumor-specific activity. The authors review rindopepimut's clinical efficacy, administration, safety, and prospects in the treatment of GBM. Expert opinion: Rindopepimut showed clinical benefit and significant efficacy in phase II clinical trials, including as part of a multi-immunotherapy approach. A phase III clinical trial was terminated early, however, as it was deemed likely the study would fail to meet its primary endpoint. Longer term and sub-group analyses will be necessary to better understand rindopepimut's future role in GBM therapy.

Authors
Elsamadicy, AA; Chongsathidkiet, P; Desai, R; Woroniecka, K; Farber, SH; Fecci, PE; Sampson, JH
MLA Citation
Elsamadicy, AA, Chongsathidkiet, P, Desai, R, Woroniecka, K, Farber, SH, Fecci, PE, and Sampson, JH. "Prospect of rindopepimut in the treatment of glioblastoma." Expert opinion on biological therapy 17.4 (April 2017): 507-513. (Review)
PMID
28274144
Source
epmc
Published In
Expert Opinion on Biological Therapy
Volume
17
Issue
4
Publish Date
2017
Start Page
507
End Page
513
DOI
10.1080/14712598.2017.1299705

Immune Constitution of Patients with Brain Tumors

© 2017 Elsevier Inc. All rights reserved. Immune deficiencies in patients with glioblastoma (GBM) are not a new discovery. Researchers have been perplexed and challenged by impairments to immunity in the context of GBM dating back to the 1970s. As immunotherapy has become both more studied and more developed, increasing evidence has highlighted factors ranging from lymphopenia to innate and cellular immune dysfunction. Much work has been done to uncover a variety of tumor-inducible mechanisms for limiting the antitumor immune response. In this chapter, we will explore the evolution of our understanding of these immune-restricting mechanisms, as well as strategies for their reversal.

Authors
Berry-Candelario, J; Farber, SH; Fecci, PE
MLA Citation
Berry-Candelario, J, Farber, SH, and Fecci, PE. "Immune Constitution of Patients with Brain Tumors." Translational Immunotherapy of Brain Tumors. March 2, 2017. 13-32.
Source
scopus
Publish Date
2017
Start Page
13
End Page
32
DOI
10.1016/B978-0-12-802420-1.00002-8

The Safety of available immunotherapy for the treatment of glioblastoma.

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Current standard of care involves maximal surgical resection combined with adjuvant chemoradiation. Growing support exists for a role of immunotherapy in treating these tumors with the goal of targeted cytotoxicity. Here we review data on the safety for current immunotherapies being tested in GBM. Areas covered: Safety data from published clinical trials, including ongoing clinical trials were reviewed. Immunotherapeutic classes currently under investigation in GBM include various vaccination strategies, adoptive T cell immunotherapy, immune checkpoint blockade, monoclonal antibodies, and cytokine therapies. Trials include children, adolescents, and adults with either primary or recurrent GBM. Expert opinion: Based on the reviewed clinical trials, the current immunotherapies targeting GBM are safe and well-tolerated with minimal toxicities which should be noted. However, the gains in patient survival have been modest. A safe and well-tolerated combinatory immunotherapeutic approach may be essential for optimal efficacy towards GBM.

Authors
Farber, SH; Elsamadicy, AA; Atik, AF; Suryadevara, CM; Chongsathidkiet, P; Fecci, PE; Sampson, JH
MLA Citation
Farber, SH, Elsamadicy, AA, Atik, AF, Suryadevara, CM, Chongsathidkiet, P, Fecci, PE, and Sampson, JH. "The Safety of available immunotherapy for the treatment of glioblastoma." Expert opinion on drug safety 16.3 (March 2017): 277-287. (Review)
PMID
27989218
Source
epmc
Published In
Expert Opinion on Drug Safety
Volume
16
Issue
3
Publish Date
2017
Start Page
277
End Page
287
DOI
10.1080/14740338.2017.1273898

Embracing rejection: Immunologic trends in brain metastasis.

Brain metastases represent the most common type of brain tumor. These tumors offer a dismal prognosis and significantly impact quality of life for patients. Their capacity for central nervous system (CNS) invasion is dependent upon induced disruptions to the blood-brain barrier (BBB), alterations to the brain microenvironment, and mechanisms for escaping CNS immunosurveillance. In the emerging era of immunotherapy, understanding how metastases are influenced by the immunologic peculiarities of the CNS will be crucial to forging therapeutic advances. In this review, the immunology of brain metastasis is explored.

Authors
Farber, SH; Tsvankin, V; Narloch, JL; Kim, GJ; Salama, AKS; Vlahovic, G; Blackwell, KL; Kirkpatrick, JP; Fecci, PE
MLA Citation
Farber, SH, Tsvankin, V, Narloch, JL, Kim, GJ, Salama, AKS, Vlahovic, G, Blackwell, KL, Kirkpatrick, JP, and Fecci, PE. "Embracing rejection: Immunologic trends in brain metastasis." Oncoimmunology 5.7 (July 2016): e1172153-. (Review)
PMID
27622023
Source
epmc
Published In
OncoImmunology
Volume
5
Issue
7
Publish Date
2016
Start Page
e1172153
DOI
10.1080/2162402x.2016.1172153

STK11/LKB1 Deficiency Promotes Neutrophil Recruitment and Proinflammatory Cytokine Production to Suppress T-cell Activity in the Lung Tumor Microenvironment.

STK11/LKB1 is among the most commonly inactivated tumor suppressors in non-small cell lung cancer (NSCLC), especially in tumors harboring KRAS mutations. Many oncogenes promote immune escape, undermining the effectiveness of immunotherapies, but it is unclear whether the inactivation of tumor suppressor genes, such as STK11/LKB1, exerts similar effects. In this study, we investigated the consequences of STK11/LKB1 loss on the immune microenvironment in a mouse model of KRAS-driven NSCLC. Genetic ablation of STK11/LKB1 resulted in accumulation of neutrophils with T-cell-suppressive effects, along with a corresponding increase in the expression of T-cell exhaustion markers and tumor-promoting cytokines. The number of tumor-infiltrating lymphocytes was also reduced in LKB1-deficient mouse and human tumors. Furthermore, STK11/LKB1-inactivating mutations were associated with reduced expression of PD-1 ligand PD-L1 in mouse and patient tumors as well as in tumor-derived cell lines. Consistent with these results, PD-1-targeting antibodies were ineffective against Lkb1-deficient tumors. In contrast, treating Lkb1-deficient mice with an IL6-neutralizing antibody or a neutrophil-depleting antibody yielded therapeutic benefits associated with reduced neutrophil accumulation and proinflammatory cytokine expression. Our findings illustrate how tumor suppressor mutations can modulate the immune milieu of the tumor microenvironment, and they offer specific implications for addressing STK11/LKB1-mutated tumors with PD-1-targeting antibody therapies.

Authors
Koyama, S; Akbay, EA; Li, YY; Aref, AR; Skoulidis, F; Herter-Sprie, GS; Buczkowski, KA; Liu, Y; Awad, MM; Denning, WL; Diao, L; Wang, J; Parra-Cuentas, ER; Wistuba, II; Soucheray, M; Thai, T; Asahina, H; Kitajima, S; Altabef, A; Cavanaugh, JD; Rhee, K; Gao, P; Zhang, H; Fecci, PE; Shimamura, T; Hellmann, MD; Heymach, JV; Hodi, FS; Freeman, GJ; Barbie, DA; Dranoff, G; Hammerman, PS; Wong, K-K
MLA Citation
Koyama, S, Akbay, EA, Li, YY, Aref, AR, Skoulidis, F, Herter-Sprie, GS, Buczkowski, KA, Liu, Y, Awad, MM, Denning, WL, Diao, L, Wang, J, Parra-Cuentas, ER, Wistuba, II, Soucheray, M, Thai, T, Asahina, H, Kitajima, S, Altabef, A, Cavanaugh, JD, Rhee, K, Gao, P, Zhang, H, Fecci, PE, Shimamura, T, Hellmann, MD, Heymach, JV, Hodi, FS, Freeman, GJ, Barbie, DA, Dranoff, G, Hammerman, PS, and Wong, K-K. "STK11/LKB1 Deficiency Promotes Neutrophil Recruitment and Proinflammatory Cytokine Production to Suppress T-cell Activity in the Lung Tumor Microenvironment." Cancer research 76.5 (March 2016): 999-1008.
PMID
26833127
Source
epmc
Published In
Cancer Research
Volume
76
Issue
5
Publish Date
2016
Start Page
999
End Page
1008
DOI
10.1158/0008-5472.can-15-1439

Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints.

Despite compelling antitumour activity of antibodies targeting the programmed death 1 (PD-1): programmed death ligand 1 (PD-L1) immune checkpoint in lung cancer, resistance to these therapies has increasingly been observed. In this study, to elucidate mechanisms of adaptive resistance, we analyse the tumour immune microenvironment in the context of anti-PD-1 therapy in two fully immunocompetent mouse models of lung adenocarcinoma. In tumours progressing following response to anti-PD-1 therapy, we observe upregulation of alternative immune checkpoints, notably T-cell immunoglobulin mucin-3 (TIM-3), in PD-1 antibody bound T cells and demonstrate a survival advantage with addition of a TIM-3 blocking antibody following failure of PD-1 blockade. Two patients who developed adaptive resistance to anti-PD-1 treatment also show a similar TIM-3 upregulation in blocking antibody-bound T cells at treatment failure. These data suggest that upregulation of TIM-3 and other immune checkpoints may be targetable biomarkers associated with adaptive resistance to PD-1 blockade.

Authors
Koyama, S; Akbay, EA; Li, YY; Herter-Sprie, GS; Buczkowski, KA; Richards, WG; Gandhi, L; Redig, AJ; Rodig, SJ; Asahina, H; Jones, RE; Kulkarni, MM; Kuraguchi, M; Palakurthi, S; Fecci, PE; Johnson, BE; Janne, PA; Engelman, JA; Gangadharan, SP; Costa, DB; Freeman, GJ; Bueno, R; Hodi, FS; Dranoff, G; Wong, K-K; Hammerman, PS
MLA Citation
Koyama, S, Akbay, EA, Li, YY, Herter-Sprie, GS, Buczkowski, KA, Richards, WG, Gandhi, L, Redig, AJ, Rodig, SJ, Asahina, H, Jones, RE, Kulkarni, MM, Kuraguchi, M, Palakurthi, S, Fecci, PE, Johnson, BE, Janne, PA, Engelman, JA, Gangadharan, SP, Costa, DB, Freeman, GJ, Bueno, R, Hodi, FS, Dranoff, G, Wong, K-K, and Hammerman, PS. "Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints." Nature communications 7 (February 17, 2016): 10501-.
PMID
26883990
Source
epmc
Published In
Nature Communications
Volume
7
Publish Date
2016
Start Page
10501
DOI
10.1038/ncomms10501

X-Ray Psoralen Activated Cancer Therapy (X-PACT).

This work investigates X-PACT (X-ray Psoralen Activated Cancer Therapy): a new approach for the treatment of solid cancer. X-PACT utilizes psoralen, a potent anti-cancer therapeutic with current application to proliferative disease and extracorporeal photopheresis (ECP) of cutaneous T Cell Lymphoma. An immunogenic role for light-activated psoralen has been reported, contributing to long-term clinical responses. Psoralen therapies have to-date been limited to superficial or extracorporeal scenarios due to the requirement for psoralen activation by UVA light, which has limited penetration in tissue. X-PACT solves this challenge by activating psoralen with UV light emitted from novel non-tethered phosphors (co-incubated with psoralen) that absorb x-rays and re-radiate (phosphoresce) at UV wavelengths. The efficacy of X-PACT was evaluated in both in-vitro and in-vivo settings. In-vitro studies utilized breast (4T1), glioma (CT2A) and sarcoma (KP-B) cell lines. Cells were exposed to X-PACT treatments where the concentrations of drug (psoralen and phosphor) and radiation parameters (energy, dose, and dose rate) were varied. Efficacy was evaluated primarily using flow cell cytometry in combination with complimentary assays, and the in-vivo mouse study. In an in-vitro study, we show that X-PACT induces significant tumor cell apoptosis and cytotoxicity, unlike psoralen or phosphor alone (p<0.0001). We also show that apoptosis increases as doses of phosphor, psoralen, or radiation increase. Finally, in an in-vivo pilot study of BALBc mice with syngeneic 4T1 tumors, we show that the rate of tumor growth is slower with X-PACT than with saline or AMT + X-ray (p<0.0001). Overall these studies demonstrate a potential therapeutic effect for X-PACT, and provide a foundation and rationale for future studies. In summary, X-PACT represents a novel treatment approach in which well-tolerated low doses of x-ray radiation are delivered to a specific tumor site to generate UVA light which in-turn unleashes both short- and potentially long-term antitumor activity of photo-active therapeutics like psoralen.

Authors
Oldham, M; Yoon, P; Fathi, Z; Beyer, WF; Adamson, J; Liu, L; Alcorta, D; Xia, W; Osada, T; Liu, C; Yang, XY; Dodd, RD; Herndon, JE; Meng, B; Kirsch, DG; Lyerly, HK; Dewhirst, MW; Fecci, P; Walder, H; Spector, NL
MLA Citation
Oldham, M, Yoon, P, Fathi, Z, Beyer, WF, Adamson, J, Liu, L, Alcorta, D, Xia, W, Osada, T, Liu, C, Yang, XY, Dodd, RD, Herndon, JE, Meng, B, Kirsch, DG, Lyerly, HK, Dewhirst, MW, Fecci, P, Walder, H, and Spector, NL. "X-Ray Psoralen Activated Cancer Therapy (X-PACT)." PloS one 11.9 (January 2016): e0162078-.
Website
http://hdl.handle.net/10161/13034
PMID
27583569
Source
epmc
Published In
PloS one
Volume
11
Issue
9
Publish Date
2016
Start Page
e0162078
DOI
10.1371/journal.pone.0162078

Peptide vaccines for the treatment of glioblastoma

© 2014, Springer Science+Business Media New York. Glioblastoma multiforme (GBM) is an extremely malignant brain tumor for which current therapies do little to remedy. Despite aggressive treatment with surgery, radiation therapy, and chemotherapy, tumors inevitably recur as a direct consequence of the infiltrative nature of GBM. The poor prognosis of patients with GBM underscores the clear and urgent need for more precise and potent therapies. Immunotherapy is emerging as a promising means to treat GBM based on the immune system’s capacity to mediate tumor-specific cytotoxicity. In this review, we will discuss the use of peptide vaccines for the treatment of GBM. The simplicity of peptide vaccines and their ability to elicit tumor antigen-specific immune responses make them an invaluable tool for the study of brain tumor immunotherapy.

Authors
Swartz, AM; Batich, KA; Fecci, PE; Sampson, JH
MLA Citation
Swartz, AM, Batich, KA, Fecci, PE, and Sampson, JH. "Peptide vaccines for the treatment of glioblastoma." Journal of Neuro-Oncology 123.3 (December 10, 2015): 433-440. (Review)
Source
scopus
Published In
Journal of Neuro-Oncology
Volume
123
Issue
3
Publish Date
2015
Start Page
433
End Page
440
DOI
10.1007/s11060-014-1676-y

Editorial: Not everything that matters can be measured and not everything that can be measured matters.

Authors
Choi, BD; Fecci, PE; Sampson, JH
MLA Citation
Choi, BD, Fecci, PE, and Sampson, JH. "Editorial: Not everything that matters can be measured and not everything that can be measured matters." Journal of neurosurgery 123.3 (September 2015): 543-544.
PMID
26115465
Source
epmc
Published In
Journal of neurosurgery
Volume
123
Issue
3
Publish Date
2015
Start Page
543
End Page
544
DOI
10.3171/2015.2.jns142977

Programmed death ligand 1 (PD-L1) as an immunotherapy target in patients with glioblastoma.

Authors
Vlahovic, G; Fecci, PE; Reardon, D; Sampson, JH
MLA Citation
Vlahovic, G, Fecci, PE, Reardon, D, and Sampson, JH. "Programmed death ligand 1 (PD-L1) as an immunotherapy target in patients with glioblastoma." Neuro-oncology 17.8 (August 2015): 1043-1045.
PMID
25964311
Source
epmc
Published In
Neuro-Oncology
Volume
17
Issue
8
Publish Date
2015
Start Page
1043
End Page
1045
DOI
10.1093/neuonc/nov071

Peptide vaccines for the treatment of glioblastoma.

Glioblastoma multiforme (GBM) is an extremely malignant brain tumor for which current therapies do little to remedy. Despite aggressive treatment with surgery, radiation therapy, and chemotherapy, tumors inevitably recur as a direct consequence of the infiltrative nature of GBM. The poor prognosis of patients with GBM underscores the clear and urgent need for more precise and potent therapies. Immunotherapy is emerging as a promising means to treat GBM based on the immune system's capacity to mediate tumor-specific cytotoxicity. In this review, we will discuss the use of peptide vaccines for the treatment of GBM. The simplicity of peptide vaccines and their ability to elicit tumor antigen-specific immune responses make them an invaluable tool for the study of brain tumor immunotherapy.

Authors
Swartz, AM; Batich, KA; Fecci, PE; Sampson, JH
MLA Citation
Swartz, AM, Batich, KA, Fecci, PE, and Sampson, JH. "Peptide vaccines for the treatment of glioblastoma." Journal of neuro-oncology 123.3 (July 2015): 433-440. (Review)
PMID
25491947
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
123
Issue
3
Publish Date
2015
Start Page
433
End Page
440
DOI
10.1007/s11060-014-1676-y

Editorial: Turning fluorescence into black and white.

Authors
Fecci, PE; Babu, R; Adamson, DC; Sampson, JH
MLA Citation
Fecci, PE, Babu, R, Adamson, DC, and Sampson, JH. "Editorial: Turning fluorescence into black and white." Journal of neurosurgery 122.6 (June 2015): 1356-1358.
PMID
25839932
Source
epmc
Published In
Journal of neurosurgery
Volume
122
Issue
6
Publish Date
2015
Start Page
1356
End Page
1358
DOI
10.3171/2014.10.jns141788

Are BiTEs the "missing link" in cancer therapy?

Conventional treatment for cancer routinely includes surgical resection and some combination of chemotherapy and radiation. These approaches are frequently accompanied by unintended and highly toxic collateral damage to healthy tissues, which are offset by only marginal prognostic improvements in patients with advanced cancers. This unfortunate balance has driven the development of novel therapies that aim to target tumors both safely and efficiently. Over the past decade, mounting evidence has supported the therapeutic utility of T-cell-centered cancer immunotherapy, which, in its various iterations, has been shown capable of eliciting highly precise and robust antitumor responses both in animal models and human trials. The identification of tumor-specific targets has further fueled a growing interest in T-cell therapies given their potential to circumvent the non-specific nature of traditional treatments. Of the several strategies geared toward achieving T-cell recognition of tumor, bispecific antibodies (bsAbs) represent a novel class of biologics that have garnered enthusiasm in recent years due to their versatility, specificity, safety, cost, and ease of production. Bispecific T-cell Engagers (BiTEs) are a subclass of bsAbs that are specific for CD3 on one arm and a tumor antigen on the second. As such, BiTEs function by recruiting and activating polyclonal populations of T-cells at tumor sites, and do so without the need for co-stimulation or conventional MHC recognition. Blinatumomab, a well-characterized BiTE, has emerged as a promising recombinant bscCD19×CD3 construct that has demonstrated remarkable antitumor activity in patients with B-cell malignancies. This clinical success has resulted in the rapid extension of BiTE technology against a greater repertoire of tumor antigens and the recent US Food and Drug Administration's (FDA) accelerated approval of blinatumomab for the treatment of a rare form of acute lymphoblastic leukemia (ALL). In this review, we dissect the role of T-cell therapeutics in the new era of cancer immunotherapy, appraise the value of CAR T-cells in the context of solid tumors, and discuss why the BiTE platform may rescue several of the apparent deficits and shortcomings of competing immunotherapies to support its widespread clinical application.

Authors
Suryadevara, CM; Gedeon, PC; Sanchez-Perez, L; Verla, T; Alvarez-Breckenridge, C; Choi, BD; Fecci, PE; Sampson, JH
MLA Citation
Suryadevara, CM, Gedeon, PC, Sanchez-Perez, L, Verla, T, Alvarez-Breckenridge, C, Choi, BD, Fecci, PE, and Sampson, JH. "Are BiTEs the "missing link" in cancer therapy?." Oncoimmunology 4.6 (June 2015): e1008339-. (Review)
PMID
26155413
Source
epmc
Published In
OncoImmunology
Volume
4
Issue
6
Publish Date
2015
Start Page
e1008339
DOI
10.1080/2162402x.2015.1008339

Immunotherapy for malignant glioma.

Malignant gliomas (MG) are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM), the most common and malignant glial tumor, die within 12-15 months. Moreover, conventional treatment, which includes surgery followed by radiation and chemotherapy, can be highly toxic by causing nonspecific damage to healthy brain and other tissues. The shortcomings of standard-of-care have thus created a stimulus for the development of novel therapies that can target central nervous system (CNS)-based tumors specifically and efficiently, while minimizing off-target collateral damage to normal brain. Immunotherapy represents an investigational avenue with the promise of meeting this need, already having demonstrated its potential against B-cell malignancy and solid tumors in clinical trials. T-cell engineering with tumor-specific chimeric antigen receptors (CARs) is one proven approach that aims to redirect autologous patient T-cells to sites of tumor. This platform has evolved dramatically over the past two decades to include an improved construct design, and these modern CARs have only recently been translated into the clinic for brain tumors. We review here emerging immunotherapeutic platforms for the treatment of MG, focusing on the development and application of a CAR-based strategy against GBM.

Authors
Suryadevara, CM; Verla, T; Sanchez-Perez, L; Reap, EA; Choi, BD; Fecci, PE; Sampson, JH
MLA Citation
Suryadevara, CM, Verla, T, Sanchez-Perez, L, Reap, EA, Choi, BD, Fecci, PE, and Sampson, JH. "Immunotherapy for malignant glioma." Surgical neurology international 6.Suppl 1 (January 2015): S68-S77.
PMID
25722935
Source
epmc
Published In
Surgical Neurology International
Volume
6
Issue
Suppl 1
Publish Date
2015
Start Page
S68
End Page
S77
DOI
10.4103/2152-7806.151341

Immunotherapy for primary brain tumors: no longer a matter of privilege.

Immunotherapy for cancer continues to gain both momentum and legitimacy as a rational mode of therapy and a vital treatment component in the emerging era of personalized medicine. Gliomas, and their most malignant form, glioblastoma, remain as a particularly devastating solid tumor for which standard treatment options proffer only modest efficacy and target specificity. Immunotherapy would seem a well-suited choice to address such deficiencies given both the modest inherent immunogenicity of gliomas and the strong desire for treatment specificity within the confines of the toxicity-averse normal brain. This review highlights the caveats and challenges to immunotherapy for primary brain tumors, as well as reviewing modalities that are currently used or are undergoing active investigation. Tumor immunosuppressive countermeasures, peculiarities of central nervous system immune access, and opportunities for rational treatment design are discussed.

Authors
Fecci, PE; Heimberger, AB; Sampson, JH
MLA Citation
Fecci, PE, Heimberger, AB, and Sampson, JH. "Immunotherapy for primary brain tumors: no longer a matter of privilege." Clinical cancer research : an official journal of the American Association for Cancer Research 20.22 (November 2014): 5620-5629. (Review)
PMID
25398845
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
20
Issue
22
Publish Date
2014
Start Page
5620
End Page
5629
DOI
10.1158/1078-0432.ccr-14-0832

Reversal of warfarin associated coagulopathy with 4-factor prothrombin complex concentrate in traumatic brain injury and intracranial hemorrhage.

Warfarin-associated intracranial hemorrhage is associated with a high mortality rate. Ongoing coagulopathy increases the likelihood of hematoma expansion and can result in catastrophic hemorrhage if surgery is performed without reversal. The current standard of care for emergency reversal of warfarin is with fresh frozen plasma (FFP). In April 2013, the USA Food and Drug Administration approved a new reversal agent, 4-factor prothrombin complex concentrate (PCC), which has the potential to more rapidly correct coagulopathy. We sought to determine the feasibility and outcomes of using PCC for neurosurgical patients. A prospective, observational study of all patients undergoing coagulopathy reversal for intracranial hemorrhage from April 2013 to December 2013 at a single, tertiary care center was undertaken. Thirty three patients underwent emergent reversal of coagulopathy using either FFP or PCC at the discretion of the treating physician. Intracranial hemorrhage included subdural hematoma, intraparenchymal hematoma, and subarachnoid hemorrhage. FFP was used in 28 patients and PCC was used in five patients. International normalized ratio at presentation was similar between groups (FFP 2.9, PCC 3.1, p=0.89). The time to reversal was significantly shorter in the PCC group (FFP 256 minutes, PCC 65 minutes, p<0.05). When operations were performed, the time delay to perform operations was also significantly shorter in the PCC group (FFP 307 minutes, PCC 159 minutes, p<0.05). In this preliminary experience, PCC appears to provide a rapid reversal of coagulopathy. Normalization of coagulation parameters may prevent further intracranial hematoma expansion and facilitate rapid surgical evacuation, thereby improving neurological outcomes.

Authors
Yanamadala, V; Walcott, BP; Fecci, PE; Rozman, P; Kumar, JI; Nahed, BV; Swearingen, B
MLA Citation
Yanamadala, V, Walcott, BP, Fecci, PE, Rozman, P, Kumar, JI, Nahed, BV, and Swearingen, B. "Reversal of warfarin associated coagulopathy with 4-factor prothrombin complex concentrate in traumatic brain injury and intracranial hemorrhage." Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 21.11 (November 2014): 1881-1884.
PMID
24953825
Source
epmc
Published In
Journal of Clinical Neuroscience
Volume
21
Issue
11
Publish Date
2014
Start Page
1881
End Page
1884
DOI
10.1016/j.jocn.2014.05.001

Antibody-based immunotherapy for malignant glioma.

Conventional therapy for malignant glioma (MG) fails to specifically eliminate tumor cells, resulting in toxicity that limits therapeutic efficacy. In contrast, antibody-based immunotherapy uses the immune system to eliminate tumor cells with exquisite specificity. Increased understanding of the pathobiology of MG and the profound immunosuppression present among patients with MG has revealed several biologic targets amenable to antibody-based immunotherapy. Novel antibody engineering techniques allow for the production of fully human antibodies or antibody fragments with vastly reduced antigen-binding dissociation constants, increasing safety when used clinically as therapeutics. In this report, we summarize the use of antibody-based immunotherapy for MG. Approaches currently under investigation include the use of antibodies or antibody fragments to: (1) redirect immune effector cells to target tumor mutations, (2) inhibit immunosuppressive signals and thereby stimulate an immunological response against tumor cells, and (3) provide costimulatory signals to evoke immunologic targeting of tumor cells. These approaches demonstrate highly compelling safety and efficacy for the treatment of MG, providing a viable adjunct to current standard-of-care therapy for MG.

Authors
Gedeon, PC; Riccione, KA; Fecci, PE; Sampson, JH
MLA Citation
Gedeon, PC, Riccione, KA, Fecci, PE, and Sampson, JH. "Antibody-based immunotherapy for malignant glioma." Seminars in oncology 41.4 (August 2014): 496-510. (Review)
PMID
25173142
Source
epmc
Published In
Seminars in Oncology
Volume
41
Issue
4
Publish Date
2014
Start Page
496
End Page
510
DOI
10.1053/j.seminoncol.2014.06.004

Immunovirotherapy for the treatment of glioblastoma

Authors
Cheema, TA; Fecci, PE; Ning, J; Rabkin, SD
MLA Citation
Cheema, TA, Fecci, PE, Ning, J, and Rabkin, SD. "Immunovirotherapy for the treatment of glioblastoma." OncoImmunology 3.1 (January 2014): e27218-e27218.
Source
crossref
Published In
OncoImmunology
Volume
3
Issue
1
Publish Date
2014
Start Page
e27218
End Page
e27218
DOI
10.4161/onci.27218

Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors.

The success in lung cancer therapy with programmed death (PD)-1 blockade suggests that immune escape mechanisms contribute to lung tumor pathogenesis. We identified a correlation between EGF receptor (EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, CTL antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased CTLs and increased markers of T-cell exhaustion in mouse models of EGFR-driven lung cancer. PD-1 antibody blockade improved the survival of mice with EGFR-driven adenocarcinomas by enhancing effector T-cell function and lowering the levels of tumor-promoting cytokines. Expression of mutant EGFR in bronchial epithelial cells induced PD-L1, and PD-L1 expression was reduced by EGFR inhibitors in non-small cell lung cancer cell lines with activated EGFR. These data suggest that oncogenic EGFR signaling remodels the tumor microenvironment to trigger immune escape and mechanistically link treatment response to PD-1 inhibition.We show that autochthonous EGFR-driven lung tumors inhibit antitumor immunity by activating the PD-1/PD-L1 pathway to suppress T-cell function and increase levels of proinflammatory cytokines. These findings indicate that EGFR functions as an oncogene through non-cell-autonomous mechanisms and raise the possibility that other oncogenes may drive immune escape.

Authors
Akbay, EA; Koyama, S; Carretero, J; Altabef, A; Tchaicha, JH; Christensen, CL; Mikse, OR; Cherniack, AD; Beauchamp, EM; Pugh, TJ; Wilkerson, MD; Fecci, PE; Butaney, M; Reibel, JB; Soucheray, M; Cohoon, TJ; Janne, PA; Meyerson, M; Hayes, DN; Shapiro, GI; Shimamura, T; Sholl, LM; Rodig, SJ; Freeman, GJ; Hammerman, PS; Dranoff, G; Wong, K-K
MLA Citation
Akbay, EA, Koyama, S, Carretero, J, Altabef, A, Tchaicha, JH, Christensen, CL, Mikse, OR, Cherniack, AD, Beauchamp, EM, Pugh, TJ, Wilkerson, MD, Fecci, PE, Butaney, M, Reibel, JB, Soucheray, M, Cohoon, TJ, Janne, PA, Meyerson, M, Hayes, DN, Shapiro, GI, Shimamura, T, Sholl, LM, Rodig, SJ, Freeman, GJ, Hammerman, PS, Dranoff, G, and Wong, K-K. "Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors." Cancer discovery 3.12 (December 2013): 1355-1363.
PMID
24078774
Source
epmc
Published In
Cancer Discovery
Volume
3
Issue
12
Publish Date
2013
Start Page
1355
End Page
1363
DOI
10.1158/2159-8290.cd-13-0310

Multifaceted oncolytic virus therapy for glioblastoma in an immunocompetent cancer stem cell model.

Glioblastoma (World Health Organization grade IV) is an aggressive adult brain tumor that is inevitably fatal despite surgery, radiation, and chemotherapy. Treatment failures are attributed to combinations of cellular heterogeneity, including a subpopulation of often-resistant cancer stem cells, aberrant vasculature, and noteworthy immune suppression. Current preclinical models and treatment strategies do not incorporate or address all these features satisfactorily. Herein, we describe a murine glioblastoma stem cell (GSC) model that recapitulates tumor heterogeneity, invasiveness, vascularity, and immunosuppressive microenvironment in syngeneic immunocompetent mice and should prove useful for a range of therapeutic studies. Using this model, we tested a genetically engineered oncolytic herpes simplex virus that is armed with an immunomodulatory cytokine, interleukin 12 (G47-mIL12). G47Δ-mIL12 infects and replicates similarly to its unarmed oncolytic herpes simplex virus counterpart in mouse 005 GSCs in vitro, whereas in vivo, it significantly enhances survival in syngeneic mice bearing intracerebral 005 tumors. Mechanistically, G47-mIL12 targets not only GSCs but also increases IFN-γ release, inhibits angiogenesis, and reduces the number of regulatory T cells in the tumor. The increased efficacy is dependent upon T cells, but not natural killer cells. Taken together, our findings demonstrate that G47Δ-mIL12 provides a multifaceted approach to targeting GSCs, tumor microenvironment, and the immune system, with resultant therapeutic benefit in a stringent glioblastoma model.

Authors
Cheema, TA; Wakimoto, H; Fecci, PE; Ning, J; Kuroda, T; Jeyaretna, DS; Martuza, RL; Rabkin, SD
MLA Citation
Cheema, TA, Wakimoto, H, Fecci, PE, Ning, J, Kuroda, T, Jeyaretna, DS, Martuza, RL, and Rabkin, SD. "Multifaceted oncolytic virus therapy for glioblastoma in an immunocompetent cancer stem cell model." Proceedings of the National Academy of Sciences of the United States of America 110.29 (July 2013): 12006-12011.
PMID
23754388
Source
epmc
Published In
Proceedings of the National Academy of Sciences of USA
Volume
110
Issue
29
Publish Date
2013
Start Page
12006
End Page
12011
DOI
10.1073/pnas.1307935110

An update on vaccine therapy and other immunotherapeutic approaches for glioblastoma.

Outcome for glioblastoma (GBM), the most common primary CNS malignancy, remains poor. The overall survival benefit recently achieved with immunotherapeutics for melanoma and prostate cancer support evaluation of immunotherapies for other challenging cancers, including GBM. Much historical dogma depicting the CNS as immunoprivileged has been replaced by data demonstrating CNS immunocompetence and active interaction with the peripheral immune system. Several glioma antigens have been identified for potential immunotherapeutic exploitation. Active immunotherapy studies for GBM, supported by preclinical data, have focused on tumor lysate and synthetic antigen vaccination strategies. Results to date confirm consistent safety, including a lack of autoimmune reactivity; however, modest efficacy and variable immunogenicity have been observed. These findings underscore the need to optimize vaccination variables and to address challenges posed by systemic and local immunosuppression inherent to GBM tumors. Additional immunotherapy strategies are also in development for GBM. Future studies may consider combinatorial immunotherapy strategies with complimentary actions.

Authors
Reardon, DA; Wucherpfennig, KW; Freeman, G; Wu, CJ; Chiocca, EA; Wen, PY; Curry, WT; Mitchell, DA; Fecci, PE; Sampson, JH; Dranoff, G
MLA Citation
Reardon, DA, Wucherpfennig, KW, Freeman, G, Wu, CJ, Chiocca, EA, Wen, PY, Curry, WT, Mitchell, DA, Fecci, PE, Sampson, JH, and Dranoff, G. "An update on vaccine therapy and other immunotherapeutic approaches for glioblastoma." Expert review of vaccines 12.6 (June 2013): 597-615. (Review)
PMID
23750791
Source
epmc
Published In
Expert Review of Vaccines
Volume
12
Issue
6
Publish Date
2013
Start Page
597
End Page
615
DOI
10.1586/erv.13.41

Regulatory T cells move in when gliomas say "I Do".

Indoleamine 2,3-dioxygenase (IDO) is an enzyme with known immunosuppressive and tolerogenic effects in cancer. Mounting evidence has associated IDO expression with the induction of regulatory T cells (Treg) and malignant progression. IDO inhibition may therefore provide a promising therapeutic approach for glioblastoma, where the need for novel treatment is great.

Authors
Choi, BD; Fecci, PE; Sampson, JH
MLA Citation
Choi, BD, Fecci, PE, and Sampson, JH. "Regulatory T cells move in when gliomas say "I Do"." Clinical cancer research : an official journal of the American Association for Cancer Research 18.22 (November 2012): 6086-6088.
PMID
23052252
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
18
Issue
22
Publish Date
2012
Start Page
6086
End Page
6088
DOI
10.1158/1078-0432.ccr-12-2801

Cancer immunoediting in malignant glioma.

Significant work from many laboratories over the last decade in the study of cancer immunology has resulted in the development of the cancer immunoediting hypothesis. This contemporary framework of the naturally arising immune system-tumor interaction is thought to comprise 3 phases: elimination, wherein immunity subserves an extrinsic tumor suppressor function and destroys nascent tumor cells; equilibrium, wherein tumor cells are constrained in a period of latency under immune control; and escape, wherein tumor cells outpace immunity and progress clinically. In this review, we address in detail the relevance of the cancer immunoediting concept to neurosurgeons and neuro-oncologists treating and studying malignant glioma by exploring the de novo immune response to these tumors, how these tumors may persist in vivo, the mechanisms by which these cells may escape/attenuate immunity, and ultimately how this concept may influence our immunotherapeutic approaches.

Authors
Dunn, GP; Fecci, PE; Curry, WT
MLA Citation
Dunn, GP, Fecci, PE, and Curry, WT. "Cancer immunoediting in malignant glioma." Neurosurgery 71.2 (August 2012): 201-222. (Review)
PMID
22353795
Source
epmc
Published In
Neurosurgery
Volume
71
Issue
2
Publish Date
2012
Start Page
201
End Page
222
DOI
10.1227/neu.0b013e31824f840d

Sequential immunotherapy by vaccination with GM-CSF-expressing glioma cells and CTLA-4 blockade effectively treats established murine intracranial tumors.

Malignant glioma is an incurable disease with a relatively short median survival. Several clinical trials have demonstrated that immunotherapy with vaccination is a safe and possibly effective way of prolonging survival. Antibody-based blockade of cytotoxic T-lymphocyte antigen 4 (CTLA-4) ligation on T lymphocytes is associated with enhanced antitumor immunity in animal models of cancer and in patients with advanced melanoma. We hypothesized that sequential therapy with granulocyte-macrophage-colony-stimulating factor (GM-CSF)-expressing whole-glioma-cell vaccination and CTLA-4 blockade is an effective strategy for treating established intracranial gliomas. GL261 glioma cells were injected into the right frontal lobes of syngeneic C57/BL6 mice. At days 3, 6, and 9 after tumor implantation, mice were treated with subcutaneous injection of irradiated GM-CSF-expressing GL261 cells. Mice were also treated with intraperitoneal injection of anti-CTLA-4 monoclonal antibodies (mAbs), either at days 3, 6, and 9 or days 12, 15, and 18. Animals were followed for survival. Splenocytes were harvested at day 22 for use in enzyme-linked immunosorbent spot assays. Early treatment of established intracranial gliomas with high-dose CTLA-4 blockade was associated with increased survival in GL261-bearing mice. Later treatment with anti-CTLA-4 monoclonal antibodies did not significantly improve survival compared with control-treated mice. Early vaccination followed by subsequent CTLA-4 blockade was associated with significantly improved survival versus either treatment alone and intensified tumor-specific immunity as measured by interferon-γ enzyme-linked immunosorbent spot assay. Sequential immunotherapy with GM-CSF-expressing irradiated glioma cells and CTLA-4 blockade synergistically prolongs survival in mice bearing established intracranial gliomas.

Authors
Agarwalla, P; Barnard, Z; Fecci, P; Dranoff, G; Curry, WT
MLA Citation
Agarwalla, P, Barnard, Z, Fecci, P, Dranoff, G, and Curry, WT. "Sequential immunotherapy by vaccination with GM-CSF-expressing glioma cells and CTLA-4 blockade effectively treats established murine intracranial tumors." Journal of immunotherapy (Hagerstown, Md. : 1997) 35.5 (June 2012): 385-389.
PMID
22576343
Source
epmc
Published In
Journal of Immunotherapy
Volume
35
Issue
5
Publish Date
2012
Start Page
385
End Page
389
DOI
10.1097/cji.0b013e3182562d59

Licorice-associated reversible cerebral vasoconstriction with PRES.

Authors
Chatterjee, N; Domoto-Reilly, K; Fecci, PE; Schwamm, LH; Singhal, AB
MLA Citation
Chatterjee, N, Domoto-Reilly, K, Fecci, PE, Schwamm, LH, and Singhal, AB. "Licorice-associated reversible cerebral vasoconstriction with PRES." Neurology 75.21 (November 2010): 1939-1941.
PMID
21098410
Source
epmc
Published In
Neurology
Volume
75
Issue
21
Publish Date
2010
Start Page
1939
End Page
1941
DOI
10.1212/wnl.0b013e3181feb299

Molecular strategies for the treatment of malignant glioma--genes, viruses, and vaccines.

The standard treatment paradigm of surgery, radiation, and chemotherapy for malignant gliomas has only a modest effect on survival. It is well emphasized in the literature that despite aggressive multimodal therapy, most patients survive approximately 1 year after diagnosis, and less than 10% survive beyond 2 years. This dismal prognosis provides the impetus for ongoing investigations in search of improved therapeutics. Standard multimodal therapy has largely reached a plateau in terms of effectiveness, and there is now a growing body of literature on novel molecular approaches for the treatment of malignant gliomas. Gene therapy, oncolytic virotherapy, and immunotherapy are the major investigational approaches that have demonstrated promise in preclinical and early clinical studies. These new molecular technologies each have distinct advantages and limitations, and none has yet demonstrated a significant survival benefit in a phase II or III clinical trial. Molecular approaches may not lead to the discovery of a "magic bullet" for these aggressive tumors, but they may ultimately prove synergistic with more conventional approaches and lead to a broadening of the multimodal approach that is the current standard of care. This review will discuss the scientific background, therapeutic potential, and clinical limitations of these novel strategies with a focus on those that have made it to clinical trials.

Authors
Selznick, LA; Shamji, MF; Fecci, P; Gromeier, M; Friedman, AH; Sampson, J
MLA Citation
Selznick, LA, Shamji, MF, Fecci, P, Gromeier, M, Friedman, AH, and Sampson, J. "Molecular strategies for the treatment of malignant glioma--genes, viruses, and vaccines." Neurosurgical review 31.2 (April 2008): 141-155. (Review)
PMID
18259789
Source
epmc
Published In
Neurosurgical Review
Volume
31
Issue
2
Publish Date
2008
Start Page
141
End Page
155
DOI
10.1007/s10143-008-0121-0

Immunotherapy of malignant brain tumors.

Despite aggressive multi-modality therapy including surgery, radiation, and chemotherapy, the prognosis for patients with malignant primary brain tumors remains very poor. Moreover, the non-specific nature of conventional therapy for brain tumors often results in incapacitating damage to surrounding normal brain and systemic tissues. Thus, there is an urgent need for the development of therapeutic strategies that precisely target tumor cells while minimizing collateral damage to neighboring eloquent cerebral cortex. The rationale for using the immune system to target brain tumors is based on the premise that the inherent specificity of immunologic reactivity could meet the clear need for more specific and precise therapy. The success of this modality is dependent on our ability to understand the mechanisms of immune regulation within the central nervous system (CNS), as well as counter the broad defects in host cell-mediated immunity that malignant gliomas are known to elicit. Recent advances in our understanding of tumor-induced and host-mediated immunosuppressive mechanisms, the development of effective strategies to combat these suppressive effects, and a better understanding of how to deliver immunologic effector molecules more efficiently to CNS tumors have all facilitated significant progress toward the realization of true clinical benefit from immunotherapeutic treatment of malignant gliomas.

Authors
Mitchell, DA; Fecci, PE; Sampson, JH
MLA Citation
Mitchell, DA, Fecci, PE, and Sampson, JH. "Immunotherapy of malignant brain tumors." Immunological reviews 222 (April 2008): 70-100. (Review)
PMID
18363995
Source
epmc
Published In
Immunological Reviews
Volume
222
Publish Date
2008
Start Page
70
End Page
100
DOI
10.1111/j.1600-065x.2008.00603.x

Systemic CTLA-4 blockade ameliorates glioma-induced changes to the CD4+ T cell compartment without affecting regulatory T-cell function.

PURPOSE: Patients with malignant glioma suffer global compromise of their cellular immunity, characterized by dramatic reductions in CD4(+) T cell numbers and function. We have previously shown that increased regulatory T cell (T(reg)) fractions in these patients explain T-cell functional deficits. Our murine glioma model recapitulates these findings. Here, we investigate the effects of systemic CTLA-4 blockade in this model. EXPERIMENTAL DESIGN: A monoclonal antibody (9H10) to CTLA-4 was employed against well-established glioma. Survival and risks for experimental allergic encephalomyelitis were assessed, as were CD4(+) T cell numbers and function in the peripheral blood, spleen, and cervical lymph nodes. The specific capacities for anti-CTLA-4 to modify the functions of regulatory versus CD4(+)CD25(-) responder T cells were evaluated. RESULTS: CTLA-4 blockade confers long-term survival in 80% of treated mice, without eliciting experimental allergic encephalomyelitis. Changes to the CD4 compartment were reversed, as anti-CTLA-4 reestablishes normal CD4 counts and abrogates increases in CD4(+)CD25(+)Foxp3(+)GITR(+) regulatory T cell fraction observed in tumor-bearing mice. CD4(+) T-cell proliferative capacity is restored and the cervical lymph node antitumor response is enhanced. Treatment benefits are bestowed exclusively on the CD4(+)CD25(-) T cell population and not T(regs), as CD4(+)CD25(-) T cells from treated mice show improved proliferative responses and resistance to T(reg)-mediated suppression, whereas T(regs) from the same mice remain anergic and exhibit no restriction of their suppressive capacity. CONCLUSIONS: CTLA-4 blockade is a rational means of reversing glioma-induced changes to the CD4 compartment and enhancing antitumor immunity. These benefits were attained through the conferment of resistance to T(reg)-mediated suppression, and not through direct effects on T(regs).

Authors
Fecci, PE; Ochiai, H; Mitchell, DA; Grossi, PM; Sweeney, AE; Archer, GE; Cummings, T; Allison, JP; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Ochiai, H, Mitchell, DA, Grossi, PM, Sweeney, AE, Archer, GE, Cummings, T, Allison, JP, Bigner, DD, and Sampson, JH. "Systemic CTLA-4 blockade ameliorates glioma-induced changes to the CD4+ T cell compartment without affecting regulatory T-cell function." Clin Cancer Res 13.7 (April 1, 2007): 2158-2167.
PMID
17404100
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
13
Issue
7
Publish Date
2007
Start Page
2158
End Page
2167
DOI
10.1158/1078-0432.CCR-06-2070

Profiling of CD4+, CD8+, and CD4+CD25+CD45RO+FoxP3+ T cells in patients with malignant glioma reveals differential expression of the immunologic transcriptome compared with T cells from healthy volunteers.

PURPOSE: Analyses of T-cell mRNA expression profiles in glioblastoma multiforme has not been previously reported but may help to define and characterize the immunosuppressed phenotype in patients with this type of cancer. EXPERIMENTAL DESIGN: We did microarray studies that have shown significant and fundamental differences in the expression profiles of CD4(+) and CD8(+) T cells and immunosuppressive CD4(+)CD25(+)CD45RO(+)FoxP3(+) regulatory T cells (T(reg)) from normal healthy volunteers compared with patients with newly diagnosed glioblastoma multiforme. For these investigations, we isolated total RNA from enriched CD4(+) and CD8(+) T cell or T(reg) cell populations from age-matched individuals and did microarray analyses. RESULTS: ANOVA and principal components analysis show that the various T cell compartments exhibit consistently similar mRNA expression profiles among individuals within either healthy or brain tumor groups but reflect significant differences between these groups. Compared with healthy volunteers, CD4(+) and CD8(+) T cells from patients with glioblastoma multiforme display coordinate down-regulation of genes involved in T cell receptor ligation, activation, and intracellular signaling. In contrast, T(regs) from patients with glioblastoma multiforme exhibit increased levels of transcripts involved in inhibiting host immunity. CONCLUSION: Our findings support the notion that key differences between expression profiles in T-cell populations from patients with glioblastoma multiforme results from differential expression of the immunologic transcriptome, such that a limited number of genes are principally important in producing the dysregulated T-cell phenotype.

Authors
Learn, CA; Fecci, PE; Schmittling, RJ; Xie, W; Karikari, I; Mitchell, DA; Archer, GE; Wei, Z; Dressman, H; Sampson, JH
MLA Citation
Learn, CA, Fecci, PE, Schmittling, RJ, Xie, W, Karikari, I, Mitchell, DA, Archer, GE, Wei, Z, Dressman, H, and Sampson, JH. "Profiling of CD4+, CD8+, and CD4+CD25+CD45RO+FoxP3+ T cells in patients with malignant glioma reveals differential expression of the immunologic transcriptome compared with T cells from healthy volunteers." Clinical cancer research : an official journal of the American Association for Cancer Research 12.24 (December 2006): 7306-7315.
PMID
17189402
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
12
Issue
24
Publish Date
2006
Start Page
7306
End Page
7315
DOI
10.1158/1078-0432.ccr-06-1727

Systemic anti-CD25 monoclonal antibody administration safely enhances immunity in murine glioma without eliminating regulatory T cells.

PURPOSE: Elevated proportions of regulatory T cells (T(reg)) are present in patients with a variety of cancers, including malignant glioma, yet recapitulative murine models are wanting. We therefore examined T(regs) in mice bearing malignant glioma and evaluated anti-CD25 as an immunotherapeutic adjunct. EXPERIMENTAL DESIGN: CD4+CD25+Foxp3+GITR+ T(regs) were quantified in the peripheral blood, spleens, cervical lymph nodes, and bone marrow of mice bearing malignant glioma. The capacities for systemic anti-CD25 therapy to deplete T(regs), enhance lymphocyte function, and generate antiglioma CTL responses were assessed. Lastly, survival and experimental allergic encephalitis risks were evaluated when anti-CD25 was combined with a dendritic cell-based immunization targeting shared tumor and central nervous system antigens. RESULTS: Similar to patients with malignant glioma, glioma-bearing mice show a CD4 lymphopenia. Additionally, CD4+CD25+Foxp3+GITR+ T(regs) represent an increased fraction of the remaining peripheral blood CD4+ T cells, despite themselves being reduced in number. Similar trends are observed in cervical lymph node and spleen, but not in bone marrow. Systemic anti-CD25 administration hinders detection of CD25+ cells but fails to completely eliminate T(regs), reducing their number only moderately, yet eliminating their suppressive function. This elimination of T(reg) function permits enhanced lymphocyte proliferative and IFN-gamma responses and up to 80% specific lysis of glioma cell targets in vitro. When combined with dendritic cell immunization, anti-CD25 elicits tumor rejection in 100% of challenged mice without precipitating experimental allergic encephalitis. CONCLUSIONS: Systemic anti-CD25 administration does not entirely eliminate T(regs) but does prevent T(reg) function. This leads to safe enhancement of tumor immunity in a murine glioma model that recapitulates the tumor-induced changes to the CD4 and T(reg) compartments seen in patients with malignant glioma.

Authors
Fecci, PE; Sweeney, AE; Grossi, PM; Nair, SK; Learn, CA; Mitchell, DA; Cui, X; Cummings, TJ; Bigner, DD; Gilboa, E; Sampson, JH
MLA Citation
Fecci, PE, Sweeney, AE, Grossi, PM, Nair, SK, Learn, CA, Mitchell, DA, Cui, X, Cummings, TJ, Bigner, DD, Gilboa, E, and Sampson, JH. "Systemic anti-CD25 monoclonal antibody administration safely enhances immunity in murine glioma without eliminating regulatory T cells." Clin Cancer Res 12.14 Pt 1 (July 15, 2006): 4294-4305.
PMID
16857805
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
12
Issue
14 Pt 1
Publish Date
2006
Start Page
4294
End Page
4305
DOI
10.1158/1078-0432.CCR-06-0053

Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma.

Immunosuppression is frequently associated with malignancy and is particularly severe in patients with malignant glioma. Anergy and counterproductive shifts toward T(H)2 cytokine production are long-recognized T-cell defects in these patients whose etiology has remained elusive for >30 years. We show here that absolute counts of both CD4(+) T cells and CD4(+)CD25(+)FOXP3(+)CD45RO(+) T cells (T(regs)) are greatly diminished in patients with malignant glioma, but T(regs) frequently represent an increased fraction of the remaining CD4 compartment. This increased T(reg) fraction, despite reduced counts, correlates with and is sufficient to elicit the characteristic manifestations of impaired patient T-cell responsiveness in vitro. Furthermore, T(reg) removal eradicates T-cell proliferative defects and reverses T(H)2 cytokine shifts, allowing T cells from patients with malignant glioma to function in vitro at levels equivalent to those of normal, healthy controls. Such restored immune function may give license to physiologic antiglioma activity, as in vivo, T(reg) depletion proves permissive for spontaneous tumor rejection in a murine model of established intracranial glioma. These findings dramatically alter our understanding of depressed cellular immune function in patients with malignant glioma and advance a role for T(regs) in facilitating tumor immune evasion in the central nervous system.

Authors
Fecci, PE; Mitchell, DA; Whitesides, JF; Xie, W; Friedman, AH; Archer, GE; Herndon, JE; Bigner, DD; Dranoff, G; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Whitesides, JF, Xie, W, Friedman, AH, Archer, GE, Herndon, JE, Bigner, DD, Dranoff, G, and Sampson, JH. "Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma." Cancer research 66.6 (March 2006): 3294-3302.
PMID
16540683
Source
epmc
Published In
Cancer Research
Volume
66
Issue
6
Publish Date
2006
Start Page
3294
End Page
3302
DOI
10.1158/0008-5472.can-05-3773

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." J Neurooncol 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors.

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.

Authors
Fecci, PE; Mitchell, DA; Archer, GE; Morse, MA; Lyerly, HK; Bigner, DD; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Archer, GE, Morse, MA, Lyerly, HK, Bigner, DD, and Sampson, JH. "The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors." Journal of neuro-oncology 64.1-2 (August 2003): 161-176. (Review)
PMID
12952297
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
64
Issue
1-2
Publish Date
2003
Start Page
161
End Page
176
DOI
10.1007/bf02700031

Adoptive immunotherapy for malignant glioma.

Despite remarkable advancements in imaging modalities and treatment options available to patients diagnosed with malignant brain tumors, the prognosis for those with high-grade lesions remains poor. The imprecise mechanisms of currently available treatments to manage these tumors do not spare damage to the normal surrounding brain and often result in major cognitive and motor deficits. Immunotherapy holds the promise of offering a potent, yet targeted, treatment to patients with brain tumors, with the potential to eradicate the malignant tumor cells without damaging normal tissues. The T cells of the immune system are uniquely capable of recognizing the altered protein expression patterns within tumor cells and mediating their destruction through a variety of effector mechanisms. Adoptive T-cell therapy is an attempt to harness and amplify the tumor-eradicating capacity of a patients' own T cells and then return these effectors to the patient in such a state that they effectively eliminate residual tumor. Although this approach is not new to the field of tumor immunology, new advancements in our understanding of T-cell activation and function and breakthroughs in tumor antigen discovery hold great promise for the translation of this modality into a clinical success.

Authors
Mitchell, DA; Fecci, PE; Sampson, JH
MLA Citation
Mitchell, DA, Fecci, PE, and Sampson, JH. "Adoptive immunotherapy for malignant glioma." Cancer journal (Sudbury, Mass.) 9.3 (May 2003): 157-166. (Review)
PMID
12952301
Source
epmc
Published In
Cancer Journal
Volume
9
Issue
3
Publish Date
2003
Start Page
157
End Page
166
DOI
10.1097/00130404-200305000-00004

Clinical immunotherapy for brain tumors.

As an immunization platform for brain tumors, dendritic cells supply an impressive host of advantages. On the simplest level, they provide the safety and tumor-specificity so wanted by current therapeutic options. Yet, in addition, as the fundamental antigen-presenting cell, they circumvent many of the immunologic challenges that gliomas and the CNS proffer and that other immunotherapeutic modes fail to overcome. Directions to take now include the identification of new tumor-specific and tumor-associated antigens; the determination of the optimal dendritic cell subtype, generation, loading method, maturation state, dose, and route of delivery for immunizations; the further characterization of dendritic cells and their activities; and, potentially, the discovery of ways to pulse dendritic cells efficiently in vivo. Preclinical studies continue to play an important role in refining this form of active immunotherapy.

Authors
Fecci, PE; Sampson, JH
MLA Citation
Fecci, PE, and Sampson, JH. "Clinical immunotherapy for brain tumors." Neuroimaging clinics of North America 12.4 (November 2002): 641-664. (Review)
PMID
12687917
Source
epmc
Published In
Neuroimaging Clinics of North America
Volume
12
Issue
4
Publish Date
2002
Start Page
641
End Page
664
DOI
10.1016/s1052-5149(02)00027-8

Viruses in the treatment of brain tumors.

The grave outlook for malignant glioma patients in spite of improvements to current modalities has ushered in new approaches to therapy. Viruses have emerged on the scene and gained attention for their ability to play essentially two roles: first, as vectors for therapeutic gene delivery and second, as engineered infectious agents capable of selectively lysing tumor cells. To date, clinical brain tumor trials using viruses for gene delivery have employed retroviral or adenoviral vectors to introduce ganciclovir susceptibility to tumors in the form of the HSV1-TK gene. Clinical oncolytic studies, on the other hand, have evaluated a conditionally replicating HSV as an antineoplastic agent. Despite some promise afforded by these trials, further studies are warranted; the investigation of additional viruses to play these roles is inevitable and is now precedented.

Authors
Fecci, PE; Gromeier, M; Sampson, JH
MLA Citation
Fecci, PE, Gromeier, M, and Sampson, JH. "Viruses in the treatment of brain tumors." Neuroimaging clinics of North America 12.4 (November 2002): 553-570. (Review)
PMID
12687911
Source
epmc
Published In
Neuroimaging Clinics of North America
Volume
12
Issue
4
Publish Date
2002
Start Page
553
End Page
570
DOI
10.1016/s1052-5149(02)00028-x

Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors

Authors
Mei, Y; Bi, WL; Greenwald, NF; Du, Z; Agar, NYR; Kaiser, UB; Woodmansee, WW; Reardon, DA; Freeman, GJ; Fecci, PE; Laws Jr, ER; Santagata, S; Dunn, GP; Dunn, IF
MLA Citation
Mei, Y, Bi, WL, Greenwald, NF, Du, Z, Agar, NYR, Kaiser, UB, Woodmansee, WW, Reardon, DA, Freeman, GJ, Fecci, PE, Laws Jr, ER, Santagata, S, Dunn, GP, and Dunn, IF. "Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors (Published online)." Oncotarget.
Source
crossref
Published In
Oncotarget
DOI
10.18632/oncotarget.12088
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Research Areas:

  • Blood-Brain Barrier
  • Brain metastasis
  • Cancer
  • Immunotherapy
  • Immunotherapy, Active
  • T cells
  • T cells--Effect of drugs on
  • T cells--Receptors