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 at 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

Administered By
Surgery, Surgical Sciences
Awarded By
Department of Defense
Role
Principal Investigator
Start Date
End Date

Publications:

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

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.” Journal of Clinical Investigation, American Society for Clinical Investigation, Jan. 2020. Crossref, doi:10.1172/jci128267.
URI
https://scholars.duke.edu/individual/pub1417508
Source
crossref
Published In
The Journal of Clinical Investigation
Published Date
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. 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

A combinatorial immunotherapy for malignant brain tumors: D2C7 immunotoxin and immune checkpoint inhibitors.

<jats:p> 102 </jats:p><jats:p> Background: Immunotoxins can induce direct and rapid cytotoxicity by targeting specific tumor antigens. D2C7 is a unique recombinant immunotoxin targeting EGFRwt/EGFRvIII, two frequently overexpressed proteins on gliomas, and is currently being tested in a phase I/II clinical trial (NCT02303678) for recurrent malignant gliomas. Immunotoxins have also been shown to induce a secondary antitumor immune response via stimulation of cytotoxic T lymphocytes (CTLs). Immune checkpoint inhibitors, which have successfully treated several advanced tumors by promoting the antitumor function of CTLs, may further enhance this immunotoxin-induced antitumor response. Thus, we hypothesize that combining D2C7 with immune checkpoint inhibitors will promote long-term tumor regression due to primary cytotoxicity and enhanced anti-tumor immunity. Methods: We developed a CT2A-mD2C7 mouse glioma cell line with robust in vitro cytotoxicity of D2C7 (IC<jats:sub>50</jats:sub>= 0.47 ng/mL). In vivo anti-tumor efficacy was evaluated by intratumoral injection of D2C7 combined with intraperitoneal injection of anti-CTLA4 or anti-PD1 antibodies in single-side and bilateral subcutaneous (SC) CT2A-mD2C7 glioma models in C57BL/6 immunocompetent mice. Results: In the single-side model, D2C7 monotherapy and combinatorial therapy showed a significant tumor growth delay (P &lt; 0.01). Complete regression ( ≥ 40%) was only observed in combinatorial therapy groups. All cured mice rejected the rechallenging of CT2A parental cells in the contralateral flank and the subsequent rechallenging of CT2A-mD2C7 cells in the brain. In the bilateral model, the larger right tumors were treated with D2C7/anti-CTLA4/anti-PD1 monotherapy or D2C7+anti-CTLA4/PD1 combinatorial therapy, while the left tumors were untreated by D2C7. In the groups where the right tumors were treated with monotherapy or combinatorial therapy, the left untreated tumors also grew much slower. Furthermore, the combinatorial therapy led to the most significantly delayed growth of the left untreated tumors (P &lt; 0.05). Conclusions: Immune checkpoint inhibitors can enhance D2C7-induced anti-tumor immunity to achieve a synergistic long-term tumor regression. </jats:p>
Authors
MLA Citation
Bao, Xuhui, et al. “A combinatorial immunotherapy for malignant brain tumors: D2C7 immunotoxin and immune checkpoint inhibitors..” Journal of Clinical Oncology, vol. 35, no. 7_suppl, American Society of Clinical Oncology (ASCO), 2017, pp. 102–102. Crossref, doi:10.1200/jco.2017.35.7_suppl.102.
URI
https://scholars.duke.edu/individual/pub1351090
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
35
Published Date
Start Page
102
End Page
102
DOI
10.1200/jco.2017.35.7_suppl.102

Messenger RNA (mRNA) nanoparticle tumour vaccination.

Use of mRNA-based vaccines for tumour immunotherapy has gained increasing attention in recent years. A growing number of studies applying nanomedicine concepts to mRNA tumour vaccination show that the mRNA delivered in nanoparticle format can generate a more robust immune response. Advances in the past decade have deepened our understanding of gene delivery barriers, mRNA's biological stability and immunological properties, and support the notion for engineering innovations tailored towards a more efficient mRNA nanoparticle vaccine delivery system. In this review we will first examine the suitability of mRNA for engineering manipulations, followed by discussion of a model framework that highlights the barriers to a robust anti-tumour immunity mediated by mRNA encapsulated in nanoparticles. Finally, by consolidating existing literature on mRNA nanoparticle tumour vaccination within the context of this framework, we aim to identify bottlenecks that can be addressed by future nanoengineering research.
Authors
Phua, KKL; Nair, SK; Leong, KW
MLA Citation
Phua, Kyle K. L., et al. “Messenger RNA (mRNA) nanoparticle tumour vaccination..” Nanoscale, vol. 6, no. 14, July 2014, pp. 7715–29. Pubmed, doi:10.1039/c4nr01346h.
URI
https://scholars.duke.edu/individual/pub1032559
PMID
24904987
Source
pubmed
Published In
Nanoscale
Volume
6
Published Date
Start Page
7715
End Page
7729
DOI
10.1039/c4nr01346h