Michael Morse

Overview:

We are studying the use of immune therapies to treat various cancers, including gastrointestinal, breast, and lung cancers and melanoma. These therapies include vaccines based on dendritic cells developed in our laboratory as well as vaccines based on peptides, viral vectors, and DNA plasmids. Our group is also a national leader in the development and use of laboratory assays for demonstrating immunologic responses to cancer vaccines. Finally, we are developing immunotherapies based on adoptive transfer of tumor and viral antigen-specific T cells.

Our current clinical trials include phase I and II studies of immunotherapy for: patients with metastatic malignancies expressing CEA, pancreatic cancer, colorectal cancer, breast cancer, and ovarian cancer, and leukemias following HSCT. My clinical area of expertise is in gastrointestinal oncology, in particular, the treatment of hepatic malignancies, and malignant melanoma.

Key words: dendritic cells, immunotherapy, vaccines, T cells, gastrointestinal oncology, melanoma, hepatoma

Positions:

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Professor in the Department of Surgery

Surgery, Surgical Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1990

Yale University

Medical Resident, Medicine

University of Washington

Fellow in Hematology-Oncology, Medicine

Duke University

Grants:

A Phase 1 multicenter, open label study of enadenotucirev combined with PD-1 inhibitor in subjects with metastatic or advanced epithelial tumors

Administered By
Duke Cancer Institute
Awarded By
PsiOxus Therapeutics Ltd.
Role
Principal Investigator
Start Date
End Date

A Randomized, Open-label, Multi-center Phase III Study of Durvalumab and Tremelimumab as First-line Treatment in Patients with Unresectable Hepatocellular Carcinoma (HIMALAYA)

Administered By
Duke Cancer Institute
Awarded By
AstraZeneca AB
Role
Principal Investigator
Start Date
End Date

A Phase 1b, Randomized, Open-Label Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) in Combination With Cisplatin Plus Gemcitabine and PEGPH20 in Combination With Atezolizumab and Cisplatin Plus Gemcitabine Compared With Cisplatin Plus Ge

Administered By
Duke Cancer Institute
Awarded By
Halozyme, Inc.
Role
Principal Investigator
Start Date
End Date

An Open-Label Multicenter Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of H3B-6527 in Subjects With Advanced Hepatocellular Carcinoma or Intrahepatic Cholangiocarcinoma

Administered By
Duke Cancer Institute
Awarded By
H3 Biomedicine, Inc.
Role
Principal Investigator
Start Date
End Date

A MULTICENTER, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF VARLITINIB PLUS CAPECITABINE VERSUS PLACEBO PLUS CAPECITABINE IN PATIENTS WITH ADVANCED OR METASTATIC BILIARY TRACT CANCER AS SECOND-LINE SYSTEMIC THERAPY

Administered By
Duke Cancer Institute
Awarded By
ASLAN Pharmaceuticals
Role
Principal Investigator
Start Date
End Date

Publications:

Expression of X-Linked Inhibitor of Apoptosis Protein (XIAP) in Breast Cancer Is Associated with Shorter Survival and Resistance to Chemotherapy.

XIAP, the most potent inhibitor of cell death pathways, is linked to chemotherapy resistance and tumor aggressiveness. Currently, multiple XIAP-targeting agents are in clinical trials. However, the characterization of XIAP expression in relation to clinicopathological variables in large clinical series of breast cancer is lacking. We retrospectively analyzed non-metastatic, non-inflammatory, primary, invasive breast cancer samples for XIAP mRNA (n = 2341) and protein (n = 367) expression. XIAP expression was analyzed as a continuous value and correlated with clinicopathological variables. XIAP mRNA expression was heterogeneous across samples and significantly associated with younger patients' age (≤50 years), pathological ductal type, lower tumor grade, node-positive status, HR+/HER2- status, and PAM50 luminal B subtype. Higher XIAP expression was associated with shorter DFS in uni- and multivariate analyses in 909 informative patients. Very similar correlations were observed at the protein level. This prognostic impact was significant in the HR+/HER2- but not in the TN subtype. Finally, XIAP mRNA expression was associated with lower pCR rate to anthracycline-based neoadjuvant chemotherapy in both uni- and multivariate analyses in 1203 informative patients. Higher XIAP expression in invasive breast cancer is independently associated with poorer prognosis and resistance to chemotherapy, suggesting the potential therapeutic benefit of targeting XIAP.
Authors
Devi, GR; Finetti, P; Morse, MA; Lee, S; de Nonneville, A; Van Laere, S; Troy, J; Geradts, J; McCall, S; Bertucci, F
MLA Citation
Devi, Gayathri R., et al. “Expression of X-Linked Inhibitor of Apoptosis Protein (XIAP) in Breast Cancer Is Associated with Shorter Survival and Resistance to Chemotherapy.Cancers (Basel), vol. 13, no. 11, June 2021. Pubmed, doi:10.3390/cancers13112807.
URI
https://scholars.duke.edu/individual/pub1484291
PMID
34199946
Source
pubmed
Published In
Cancers
Volume
13
Published Date
DOI
10.3390/cancers13112807

Immune Checkpoint Combinations with Inflammatory Pathway Modulators

Immune checkpoint inhibition of program death protein-1 (PD-1) and its ligands PD-L1 and PD-L2 is an established therapeutic modality in melanoma, non-small cell lung cancer, renal cell carcinoma, and other tumor types. Unfortunately, 60 to 80% of all patients experience disease progression and become refractory to immune checkpoint therapies. Broadly, mechanisms of immune checkpoint inhibitor resistance can be categorized as presence of oncogenic driver mutations, severe T cell exhaustion, neoantigen burden, epigenetic alterations, or mutations involved in critical pathways including PTEN, JAK, or Wnt signaling. The dysregulation of inflammatory signaling pathways (namely, genes involved in angiogenesis, chemotaxis, matrix remodeling, wound healing, and mesenchymal transition) is of critical importance to response to immune checkpoint therapies. Inflammatory cytokine signaling pathways exert downstream effects on immunosuppressive elements such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) which inhibit the function of effector T cells, NK cells, and dendritic cells, promoting immune tolerance and tumor growth. We herein review three targets for inflammatory pathway modulation: indoleamine 2,3-dioxygenase (IDO), transforming growth factor β (TGFβ), and adenosine. Targeting these pathways may address the unmet need to develop novel therapeutic approaches to increase response rates to immune checkpoint inhibitors and improve clinical outcomes.
MLA Citation
DeVito, N., et al. “Immune Checkpoint Combinations with Inflammatory Pathway Modulators.” Current Cancer Research, 2018, pp. 219–41. Scopus, doi:10.1007/978-3-319-63757-0_8.
URI
https://scholars.duke.edu/individual/pub1494214
Source
scopus
Published Date
Start Page
219
End Page
241
DOI
10.1007/978-3-319-63757-0_8

Immunotherapy in gastrointestinal malignancies

Recent reports of efficacy of immune therapies in solid tumors other than melanoma and renal cell carcinoma have raised enthusiasm for testing immunotherapy in gastrointestinal (GI) malignancies. Strategies under development include antibodies and related molecules that mediate cellular cytotoxicity, vaccines intended to activate tumor-specific T cell and antibody responses, adoptive transfer of natural killer (NK) cells, tumor infiltrating lymphocytes, and chimeric antigen receptor T cells, and immunomodulatory drugs such as checkpoint blocking antibodies. Thus far, benefit has been modest although insights from these studies have provided new directions for testing. We will review the current status of the various immunotherapy approaches undergoing testing in GI malignancies.
Authors
MLA Citation
Morse, M. A. “Immunotherapy in gastrointestinal malignancies.” MULTIDISCIPLINARY MANAGEMENT OF GASTROINTESTINAL CANCERS, 2016, pp. 27–69. Scopus, doi:10.1142/9789814651875_0002.
URI
https://scholars.duke.edu/individual/pub1500848
Source
scopus
Published Date
Start Page
27
End Page
69
DOI
10.1142/9789814651875_0002

Clinical efficacy of intra-cavitary infusions of autologous dendritic cell/cytokine-induced killer cell products for the treatment of refractory malignant pleural effusions and ascites.

To explore the safety and efficacy of intra-cavitary infusions of autologous mixed dendritic cell (DC)-cytokine-induced killer (CIK) cell products in advanced cancer patients with malignant pleural effusions or ascites. DC-CIKs were expanded ex vivo (mean yield of 1.36×109 cells (range, 0.74~4.98×109)) from peripheral blood mononuclear cells obtained by repeated venipuncture or apheresis. Patients received at least 1 cycle of 3 infusions of the DC-CIKs administered by indwelling catheter into the pleural or peritoneal cavity every other day. The volume of malignant effusions was assessed radiologically. Peripheral blood lymphocyte populations were enumerated by flow cytometry. Quality of life (QoL) during the DC-CIK infusions was assessed by the EORTC QLQ-30 instrument. ctDNA sequencing was performed to analyze gene clonal load and molecular tumor burden during the infusion treatment. Thirty-seven patients with breast, lung and other malignancies were enrolled. The results showed that intra-cavitary DC-CIK infusions (16 intrapleural and 21 intraperitoneal) were well-tolerated with no grade 3/4 adverse events. There was one complete response with effusion disappearance (CR) (3%), 13 partial responses (PR) (35%), 12 with stable disease (SD) (32%) and 11 with progressive disease (PD) (30%), resulting in a clinical effusion control rate (CCR) of 70% (26/37). The total number of infused CIKs and the CD3+/CD8+ and CD8+/CD28+ T cell frequencies within the CIKs were associated with effusion control (P=0.013). Moreover, increased peripheral blood CD3+/CD8+ (P=0.035) and decreased CD4+/CD25+ T cell frequencies (P=0.041) following the DC-CIK infusions were associated with malignant effusion and ascites control. Reductions in ctDNA correlated with clinical benefit. In conclusion, intra-cavitary autologous cellular immunotherapy is an alternative method to effectively control malignant pleural effusions and ascites. The overall effusion control rate was associated with higher peripheral blood effector T cell frequencies.
Authors
He, Z; Wang, S; Qiao, G; Wang, X; Zhou, X; Zhu, S; Yuan, Y; Morse, MA; Hobeika, A; Ren, J; Lyerly, HK
URI
https://scholars.duke.edu/individual/pub1454060
PMID
32774747
Source
pubmed
Published In
American Journal of Translational Research
Volume
12
Published Date
Start Page
3940
End Page
3952

Targeting the glucagon receptor signaling pathway as a novel strategy to counteract PI3K inhibitor induced hyperglycemia while sustaining tumor PI3K inhibition.

Authors
Wang, J; Osada, T; Morse, MA; Calzone, F; Yan, H; Thai, D; Lyerly, HK
MLA Citation
Wang, Jie, et al. “Targeting the glucagon receptor signaling pathway as a novel strategy to counteract PI3K inhibitor induced hyperglycemia while sustaining tumor PI3K inhibition.Leuk Lymphoma, vol. 62, no. 7, July 2021, pp. 1761–64. Pubmed, doi:10.1080/10428194.2021.1881504.
URI
https://scholars.duke.edu/individual/pub1474786
PMID
33576297
Source
pubmed
Published In
Leuk Lymphoma
Volume
62
Published Date
Start Page
1761
End Page
1764
DOI
10.1080/10428194.2021.1881504