Pancreatic cancer kills nearly 50,000 people each year. Despite decades of research and numerous clinical trials, there are still no effective treatments and the median survival time is under six months. Unlike in other solid tumors, checkpoint immunotherapies have demonstrated minimal clinical benefit in pancreatic cancer and often trigger severe adverse events in patients. Given the high mortality rate of pancreatic cancer and the limited efficacy of current immunotherapy approaches, Dr. Sanjana proposes to use massively-parallel genome engineering to comprehensively map all genes that can boost immune responses to pancreatic cancer. These findings will enable the development of next-generation T cell therapies that are more potent for difficult-to-treat cancers like pancreatic cancer.
First, he will activate each of the roughly 20,000 genes in human T cells to pinpoint the genes that enhance immunotherapy responses in pancreatic cancer. He will do this using T cells in normal conditions as well as in the presence of immunosuppressive and inflammatory cues that mimic the challenging conditions in the pancreatic tumor environment. Next, Dr. Sanjana will verify that the genes identified block T cell exhaustion using different human pancreatic cancer cell lines, mouse models that capture the poor immune infiltration that is a hallmark of pancreatic cancer, and single-cell profiling across different subtypes of primary T cells. Taken together, this broadly-applicable technology platform will lead to a deeper understanding of the cell types and mechanisms by which particular genes enhance immunotherapy.
Projects and Grants
A High-Throughput Approach to Overcome T Cell Immunosuppression in Pancreatic Cancers
New York Genome Center | Pancreatic Cancer | 2020
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