Neeha Zaidi
Developing vaccines to treat & prevent pancreatic cancer
Assistant Professor
Department of Oncology
School of Medicine
Research Overview
My research focuses on the development of vaccines for the treatment and prevention of pancreatic cancer. We have developed a vaccine that targets the earliest oncogene in pancreatic cancer – mutated KRAS. Our vaccine is currently being tested in the clinic for patients with pancreas cancer, as well as those individuals who are at risk for developing pancreatic cancer. We utilize both mouse models and human samples to characterize the immune responses elicited by our antigen-targeted vaccines in order to both elucidate mechanisms of response and to develop novel combination immunotherapy strategies to enhance anti-tumor immunity. Recent efforts have included identifying and enriching for CD4+ activating neoantigens and using cutting–edge molecular dynamics to improve the prediction of candidate neoantigens. The second area of our research program is to characterize the immune compartment of the evolving precancerous microenvironment in order to fine-tune our vaccination approach by modulating the earliest inflammatory changes in the microenvironment. Together these studies will allow us to understand mechanisms of vaccine-induced responses and to identify inhibitory signals that we may need to bypass in the evolving pancreas cancer and precancer immune microenvironment.
Selected Publications
- Huff AL, Longway G, Mitchell JT, Andaloori L, Davis-Marcisak E, Chen F, Lyman MR, Wang R, Mathew J, Barrett B, Rahman S, Leatherman J, Yarchoan M, Azad NS, Yegnasubramanian S, Kagohara LT, Fertig EJ, Jaffee EM, Armstrong TD, Zaidi N. CD4 T cell-activating neoantigens enhance personalized cancer vaccine efficacy. Journal of Clinical Investigation Insight, 2023.
- Jayaraman S, Montagne JM, Nirschl TR, Marcisak E, Johnson J, Huff A, Hsiao MH, Nauroth J, Heumann T, Zarif JC, Jaffee EM, Azad N, Fertig EJ, Zaidi N, Larman HB. Barcoding intracellular reverse transcription enables high-throughput phenotype-coupled T cell receptor analyses. Cell Reports Methods, 2023.
- Zaidi N, Soban M, Chen F, Kinkead H, Mathew J, Yarchoan M, Armstrong TD, Haider S, Jaffee EM. Role of in silico structural modeling in predicting immunogenic neoepitopes for cancer vaccine development. Journal of Clinical Investigation Insight, 2020.
- Kinkead HL, Hopkins A, Lutz E, Wu AA, Yarchoan M, Cruz K, Woolman S, Vithayathil T, Glickman LH, Ndubaku CO, McWhirter SM, Dubensky TW Jr, Armstrong TD, Jaffee EM, Zaidi N. Combining STING-based neoantigen-targeted vaccine with checkpoint modulators enhances antitumor immunity in murine pancreatic cancer. Journal of Clinical Investigation Insight, 2018.
- Delitto D, Zabransky DJ, Chen F, Thompson ED, Zimmerman JW, Armstrong TD, Leatherman JM, Suri R, Lopez-Vidal TY, Huff AL, Lyman MR, Guinn SR, Baretti M, Kagohara LT, Ho WJ, Azad NS, Burns WR, He J, Wolfgang CL, Burkhart RA, Zheng L, Yarchoan M, Zaidi N, Jaffee EM. Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection. Oncoimmunology, 2021.