Date Posted/Aired
Presented By Neeha Zaidi, M.D.
Speaker
Neeha Zaidi, M.D.
Assistant Professor of Oncology
Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins University
Neeha Zaidi is a physician-scientist and oncologist who focuses on the development of vaccine strategies for the treatment and interception of pancreatic cancer. Specifically, her work focuses on targeting mutated KRAS which is expressed in up to 90% of pancreatic cancers as well as associated precursor lesions. She is leading the first trial to test a mutant KRAS vaccine for pancreatic cancer interception in high–risk cohorts either with germline predisposition and/or high–risk intrapapillary mucinous neoplasia. Their work utilizes single cell technologies to analyze the vaccine-induced T cell transcriptome and repertoire, as well as spatial transcriptomics to assess changes in the cellular architecture in premalignant tissue. In tandem, mouse models are used to test strategies to enhance vaccine efficacy by (a) identifying MHC II neoantigens; (b) using molecular dynamics to predict immunogenic neoantigens; and (c) studying the temporal sequence of changes in cellular composition as premalignancy progresses to PDAC.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) remains a deadly disease and is projected to be the third leading cause of death by 2030. Contemporary immunotherapies have shown little to now response in PDAC. However, we and others find the premalignant lesions PanINs (or pancreatic intraepithelial neoplasia) are less immunosuppressive and more amenable to vaccine interception strategies. Mutated KRAS is the earliest driver that is expressed in up to 90% of precursor lesions and thus serves as an attractive off-the-shelf vaccine target for interception. Notably, at least 10% of PDACs arise from a genetic predisposition. We have tested a pooled long peptide vaccine targeting the six most common KRAS mutations in high-risk cohorts after establishing both safety and immunogenicity in patients who had undergone PDAC resection and received standard-of-care adjuvant chemotherapy. In both studies, we have demonstrated an induction of de novo, high quality T cell responses post-vaccination.
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