Smita Nair

Overview:

I have 22 years of experience in the field of cancer vaccines and immunotherapy and I am an accomplished T cell immunologist. Laboratory website:
https://surgery.duke.edu/immunology-inflammation-immunotherapy-laboratory

Current projects in the Nair Laboratory:
1] Dendritic cell vaccines using tumor-antigen encoding RNA (mRNA, total tumor RNA, amplified tumor mRNA)
2] Local immune receptor modulation using mRNA that encodes for antibodies, receptor-ligands, cytokines, chemokines and toll-like receptors (current target list: CTLA4, GITR, PD1, TIM3, LAG3, OX40 and 41BB)
3] Combination therapies for cancer: cytotoxic therapy (radiation, chemo and oncolytic poliovirus therapy) with dendritic cell-based vaccines and immune checkpoint blockade
4] Adoptive T cell therapy using tumor RNA-transfected dendritic cells to expand tumor-specific T cells ex vivo
5] Adoptive T cell therapy using PSMA CAR (chimeric antigen receptor) RNA-transfected T cells
6] Direct injection of tumor antigen encoding RNA (targeting antigens to dendric cells in vivo using nanoparticles and aptamers)

Positions:

Professor in Surgery

Surgery, Surgical Sciences
School of Medicine

Professor in Pathology

Pathology
School of Medicine

Professor in Neurosurgery

Neurosurgery
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1993

University of Tennessee, Knoxville

Grants:

Innate Antiviral Signals for Cancer Immunotherapy

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Oncolytic Polovirus, Immunotoxin, and Checkpoint Inhibitor Therapy of Gliomas

Administered By
Neurosurgery, Neuro-Oncology Clinical Research
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Cancer Immunotherapy Through Intratumoral Activation of Recall Responses

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Co-Sponsor
Start Date
End Date

Melanoma-mediated Dendritic Cell Tolerization and Immune Evasion

Administered By
Medicine, Medical Oncology
Awarded By
National Institutes of Health
Role
Co-Mentor
Start Date
End Date

Metabolic Reprogramming of Dendritic Cell-based Cancer Vaccines to Enhance Anti-Tumor Immunity

Administered By
Medicine, Medical Oncology
Awarded By
Alliance for Cancer Gene Therapy
Role
Mentor
Start Date
End Date

Publications:

Multiplexed, quantitative serological profiling of COVID-19 from a drop of blood by a point-of-care test.

Highly sensitive, specific, and point-of-care (POC) serological assays are an essential tool to manage the COVID-19 pandemic. Here, we report on a microfluidic, multiplexed POC test that can profile the antibody response against multiple SARS-CoV-2 antigens - Spike S1 (S1), Nucleocapsid (N), and the receptor binding domain (RBD) - simultaneously from a 60 microliter drop of blood, plasma, or serum. We assessed the levels of anti-SARS-CoV-2 antibodies in plasma samples from 19 individuals (at multiple time points) with COVID-19 that required admission to the intensive care unit and from 10 healthy individuals. This POC assay shows good concordance with a live virus microneutralization assay, achieved high sensitivity (100%) and specificity (100%), and successfully tracked the longitudinal evolution of the antibody response in infected individuals. We also demonstrated that we can detect a chemokine, IP-10, on the same chip, which may provide prognostic insight into patient outcomes. Because our test requires minimal user intervention and is read by a handheld detector, it can be globally deployed in the fight against COVID-19 by democratizing access to laboratory quality tests.
Authors
Heggestad, JT; Kinnamon, DS; Olson, LB; Liu, J; Kelly, G; Wall, SA; Fontes, CM; Joh, DY; Hucknall, AM; Pieper, C; Naqvi, IA; Chen, L; Que, LG; Oguin, T; Nair, SK; Sullenger, BA; Woods, CW; Sempowski, GD; Kraft, BD; Chilkoti, A
MLA Citation
Heggestad, Jacob T., et al. “Multiplexed, quantitative serological profiling of COVID-19 from a drop of blood by a point-of-care test.Medrxiv, Nov. 2020. Pubmed, doi:10.1101/2020.11.05.20226654.
URI
https://scholars.duke.edu/individual/pub1487524
PMID
33173900
Source
pubmed
Published In
Medrxiv
Published Date
DOI
10.1101/2020.11.05.20226654

Clinical Profile of Neonates with Hypernatremic Dehydration in an Outborn Neonatal Intensive Care Unit.

This hospital-record review describes the clinical profile of hypernatremic dehydration in neonates. 49 neonates (3.4% of the total admitted newborns) developed hypernatremic dehydration between January 2014 and August 2015. The major presenting complaints were fever (34.6%), poor feeding (42.8%), loose stools (40.8%) and lethargy (26.5%). The mean (SD) time needed for correction of hypernatremia was 38.6 (15.1) hours. Exclusively breastfed neonates had lesser complication rates of hypernatremic dehydration.
Authors
Nair, S; Singh, A; Jajoo, M
MLA Citation
Nair, Smita, et al. “Clinical Profile of Neonates with Hypernatremic Dehydration in an Outborn Neonatal Intensive Care Unit.Indian Pediatr, vol. 55, no. 4, Apr. 2018, pp. 301–05.
URI
https://scholars.duke.edu/individual/pub1488969
PMID
29428916
Source
pubmed
Published In
Indian Pediatr
Volume
55
Published Date
Start Page
301
End Page
305

Research Letters

Authors
Nair, S; Singh, A; Jajoo, M; Yadav, P; Sharma, P; Arora, R
MLA Citation
Nair, S., et al. “Research Letters.” Indian Pediatrics, vol. 55, no. 4, Apr. 2018, pp. 343–45. Scopus, doi:10.1007/s13312-018-1268-6.
URI
https://scholars.duke.edu/individual/pub1488970
Source
scopus
Published In
Indian Pediatrics
Volume
55
Published Date
Start Page
343
End Page
345
DOI
10.1007/s13312-018-1268-6

Breast cancer-derived DAMPs enhance cell invasion and metastasis, while nucleic acid scavengers mitigate these effects.

Breast cancer (BC) is the most common malignancy in women. Particular subtypes with aggressive behavior are major contributors to poor outcomes. Triple-negative breast cancer (TNBC) is difficult to treat, pro-inflammatory, and highly metastatic. We demonstrate that TNBC cells express TLR9 and are responsive to TLR9 ligands, and treatment of TNBC cells with chemotherapy increases the release of nucleic-acid-containing damage-associated molecular patterns (NA DAMPs) in cell culture. Such culture-derived and breast cancer patient-derived NA DAMPs increase TLR9 activation and TNBC cell invasion in vitro. Notably, treatment with the polyamidoamine dendrimer generation 3.0 (PAMAM-G3) behaved as a nucleic acid scavenger (NAS) and significantly mitigates such effects. In mice that develop spontaneous BC induced by polyoma middle T oncoprotein (MMTV-PyMT), treatment with PAMAM-G3 significantly reduces lung metastasis. Thus, NAS treatment mitigates cancer-induced inflammation and metastasis and represents a novel therapeutic approach for combating breast cancer.
Authors
Eteshola, EOU; Landa, K; Rempel, RE; Naqvi, IA; Hwang, ES; Nair, SK; Sullenger, BA
MLA Citation
Eteshola, Elias O. U., et al. “Breast cancer-derived DAMPs enhance cell invasion and metastasis, while nucleic acid scavengers mitigate these effects.Mol Ther Nucleic Acids, vol. 26, Dec. 2021, pp. 1–10. Pubmed, doi:10.1016/j.omtn.2021.06.016.
URI
https://scholars.duke.edu/individual/pub1496637
PMID
34513289
Source
pubmed
Published In
Molecular Therapy. Nucleic Acids
Volume
26
Published Date
Start Page
1
End Page
10
DOI
10.1016/j.omtn.2021.06.016

β-Cyclodextrin-containing polymer treatment of cutaneous lupus and influenza improves outcomes.

Nucleic acid (NA)-containing damage- and pathogen-associated molecular patterns (DAMPs and PAMPs, respectively) are implicated in numerous pathological conditions from infectious diseases to autoimmune disorders. Nucleic acid-binding polymers, including polyamidoamine (PAMAM) dendrimers, have demonstrated anti-inflammatory properties when administered to neutralize DAMPs/PAMPs. The PAMAM G3 variant has been shown to have beneficial effects in a cutaneous lupus erythematosus (CLE) murine model and improve survival of mice challenged with influenza. Unfortunately, the narrow therapeutic window of cationic PAMAM dendrimers makes their clinical development challenging. An alternative nucleic acid-binding polymer that has been evaluated in humans is a linear β-cyclodextrin-containing polymer (CDP). CDP's characteristics prompted us to evaluate its anti-inflammatory potential in CLE autoimmune and influenza infectious disease mouse models. We report that CDP effectively inhibits NA-containing DAMP-mediated activation of Toll-like receptors (TLRs) in cell culture, improves healing in lupus mice, and does not immunocompromise treated animals upon influenza infection but improves survival even when administered 3 days after infection. Finally, as anticipated, we observe limited toxicity in animals treated with CDP compared with PAMAM G3. Thus, CDP is a new anti-inflammatory agent that may be readily translated to the clinic to combat diseases associated with pathological NA-containing DAMPs/PAMPs.
Authors
Kelly, L; Olson, LB; Rempel, RE; Everitt, JI; Levine, D; Nair, SK; Davis, ME; Sullenger, BA
MLA Citation
Kelly, Linsley, et al. “β-Cyclodextrin-containing polymer treatment of cutaneous lupus and influenza improves outcomes.Mol Ther, Oct. 2021. Pubmed, doi:10.1016/j.ymthe.2021.10.003.
URI
https://scholars.duke.edu/individual/pub1498125
PMID
34628051
Source
pubmed
Published In
Molecular Therapy : the Journal of the American Society of Gene Therapy
Published Date
DOI
10.1016/j.ymthe.2021.10.003