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

Novel Immune Modulating Cellular Vaccine for Prostate Cancer Immunotherapy

Awarded By
Department of Defense
Role
Principal Investigator
Start Date
End Date

Publications:

Blocking proinvasive signaling and inflammatory activation in triple-negative breast cancer with nucleic-acid scavengers (NAS).

Authors
Eteshola, EOU; Landa, K; Hwang, ES; Moreno, A; Nair, SK; Sullenger, BA
MLA Citation
Eteshola, Elias O. U., et al. “Blocking proinvasive signaling and inflammatory activation in triple-negative breast cancer with nucleic-acid scavengers (NAS).Cancer Immunology Research, vol. 8, no. 3, AMER ASSOC CANCER RESEARCH, 2020, pp. 76–76.
URI
https://scholars.duke.edu/individual/pub1434819
Source
wos
Published In
Cancer Immunology Research
Volume
8
Published Date
Start Page
76
End Page
76

Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity.

Viruses naturally engage innate immunity, induce antigen presentation, and mediate CD8 T cell priming against foreign antigens. Polioviruses can provide a context optimal for generating antigen-specific CD8 T cells, as they have natural tropism for dendritic cells, preeminent inducers of CD8 T cell immunity; elicit Th1-promoting inflammation; and lack interference with innate or adaptive immunity. However, notorious genetic instability and underlying neuropathogenicity has hampered poliovirus-based vector applications. Here we devised a strategy based on the polio:rhinovirus chimera PVSRIPO, devoid of viral neuropathogenicity after intracerebral inoculation in human subjects, for stable expression of exogenous antigens. PVSRIPO vectors infect, activate, and induce epitope presentation in DCs in vitro; they recruit and activate DCs with Th1-dominant cytokine profiles at the injection site in vivo. They efficiently prime tumor antigen-specific CD8 T cells in vivo, induce CD8 T cell migration to the tumor site, delay tumor growth and enhance survival in murine tumor models.
Authors
Mosaheb, MM; Dobrikova, EY; Brown, MC; Yang, Y; Cable, J; Okada, H; Nair, SK; Bigner, DD; Ashley, DM; Gromeier, M
MLA Citation
Mosaheb, Mubeen M., et al. “Genetically stable poliovirus vectors activate dendritic cells and prime antitumor CD8 T cell immunity.Nat Commun, vol. 11, no. 1, Jan. 2020, p. 524. Pubmed, doi:10.1038/s41467-019-13939-z.
URI
https://scholars.duke.edu/individual/pub1428870
PMID
31988324
Source
pubmed
Published In
Nature Communications
Volume
11
Published Date
Start Page
524
DOI
10.1038/s41467-019-13939-z

Abstract 4515: Utilizing nucleic-acid scavengers (NASs) to inhibit proinflammatory and proinvasive signaling in triple-negative breast cancer

Authors
Eteshola, EO; Naqvi, IA; Gunaratne, R; Moreno, A; Nair, SK; Sullenger, BA
MLA Citation
Eteshola, Elias O., et al. “Abstract 4515: Utilizing nucleic-acid scavengers (NASs) to inhibit proinflammatory and proinvasive signaling in triple-negative breast cancer.” Tumor Biology, American Association for Cancer Research, 2019. Crossref, doi:10.1158/1538-7445.am2019-4515.
URI
https://scholars.duke.edu/individual/pub1416467
Source
crossref
Published In
Tumor Biology
Published Date
DOI
10.1158/1538-7445.am2019-4515

Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses.

Efficacy of dendritic cell (DC) cancer vaccines is classically thought to depend on their antigen-presenting cell (APC) activity. Studies show, however, that DC vaccine priming of cytotoxic T lymphocytes (CTLs) requires the activity of endogenous DCs, suggesting that exogenous DCs stimulate antitumor immunity by transferring antigens (Ags) to endogenous DCs. Such Ag transfer functions are most commonly ascribed to monocytes, implying that undifferentiated monocytes would function equally well as a vaccine modality and need not be differentiated to DCs to be effective. Here, we used several murine cancer models to test the antitumor efficacy of undifferentiated monocytes loaded with protein or peptide Ag. Intravenously injected monocytes displayed antitumor activity superior to DC vaccines in several cancer models, including aggressive intracranial glioblastoma. Ag-loaded monocytes induced robust CTL responses via Ag transfer to splenic CD8+ DCs in a manner independent of monocyte APC activity. Ag transfer required cell-cell contact and the formation of connexin 43-containing gap junctions between monocytes and DCs. These findings demonstrate the existence of an efficient gap junction-mediated Ag transfer pathway between monocytes and CD8+ DCs and suggest that administration of tumor Ag-loaded undifferentiated monocytes may serve as a simple and efficacious immunotherapy for the treatment of human cancers.
Authors
Huang, M-N; Nicholson, LT; Batich, KA; Swartz, AM; Kopin, D; Wellford, S; Prabhakar, VK; Woroniecka, K; Nair, SK; Fecci, PE; Sampson, JH; Gunn, MD
MLA Citation
Huang, Min-Nung, et al. “Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses.J Clin Invest, vol. 130, no. 2, Feb. 2020, pp. 774–88. Pubmed, doi:10.1172/JCI128267.
URI
https://scholars.duke.edu/individual/pub1417508
PMID
31661470
Source
pubmed
Published In
J Clin Invest
Volume
130
Published Date
Start Page
774
End Page
788
DOI
10.1172/JCI128267

Examining Peripheral and Tumor Cellular Immunome in Patients With Cancer.

Immunotherapies are rapidly being integrated into standard of care (SOC) therapy in conjunction with surgery, chemotherapy, and radiotherapy for many cancers and a large number of clinical studies continue to explore immunotherapy alone and as part of combination therapies in patients with cancer. It is evident that clinical effectiveness of immunotherapy is limited to a subset of patients and improving immunotherapy related outcomes remains a major scientific and clinical effort. Understanding the immune cell subset phenotype and activation/functional status (cellular immunome) prior to and post therapy is therefore critical to develop biomarkers that (1) will predict if a patient will respond to immunotherapy and (2) are a result of immunotherapy. In this study, we investigated local (tumor) and peripheral (blood) cellular immunome of patients with melanoma, breast cancer, and brain cancer using a rapid and reliable standardized, multiparameter flow cytometry assay. We used this approach to monitor changes in the peripheral cellular immunome in women with breast cancer undergoing SOC therapy. Our analysis is unique because it is conducted using matched fresh tumor tissue and blood from patients in real-time, within 2-3 h of sample acquisition, and provides insight into the innate and adaptive immune cell profile in blood and tumor. Specific to blood, this approach involves no manipulation and evaluates all immune subsets such as T cells, B cells, natural killer (NK) cells, monocytes, dendritic cells (DCs), neutrophils, eosinophils, and basophils using 0.5 ml of blood. Analysis of the corresponding tumor provides much needed insight into the phenotype and activation status of immune cells, especially T and B cells, in the tumor microenvironment vs. the periphery. This analysis will be used to assess baseline and therapy-mediated changes in local and peripheral cellular immunome in patients with glioblastoma, breast cancer, and melanoma in planned immunotherapy clinical studies.
Authors
Holl, EK; Frazier, VN; Landa, K; Beasley, GM; Hwang, ES; Nair, SK
MLA Citation
Holl, Eda K., et al. “Examining Peripheral and Tumor Cellular Immunome in Patients With Cancer.Front Immunol, vol. 10, 2019, p. 1767. Pubmed, doi:10.3389/fimmu.2019.01767.
URI
https://scholars.duke.edu/individual/pub1404042
PMID
31417550
Source
pubmed
Published In
Frontiers in Immunology
Volume
10
Published Date
Start Page
1767
DOI
10.3389/fimmu.2019.01767