Shivani Srivastava, PhD

Bob Bast Translational Research Grant *

Our lab is developing treatments for human cancers by engineering immune cells called “T cells” to recognize and kill tumor cells. Engineered T cells can eradicate tumors in patients with blood cancers, like leukemia and lymphoma. However, they have had limited success so far against more common “solid tumors”, like breast and lung cancer, which are responsible for the majority of cancer deaths. Solid tumors can evade attack by inducing T cells to lose function and become “exhausted.” Strategies to preserve T cell function, thus, are needed to extend the success of engineered T cell therapy to solid tumors. Our lab has developed a mouse model of lung cancer that mimics human tumor development and patient response to therapy. In this model, T cells engineered to overexpress a gene that promotes T cell function dramatically eliminated tumors in ~50% of mice. Based partly on these results, a clinical trial is being planned to test whether these T cells are safe and effective in patients. However, our data show that tumors still progress in ~50% of mice. We will use the mouse model we developed to define why tumors progress in a subset of mice and test different combination treatments to identify regimens that improve T cell function and kill tumors most effectively. Working with Fred Hutch clinicians and industry partners, our goal is to translate the strategies that appear most effective in mouse models to the clinic to test their impact in patients.    

Location: Fred Hutchinson Cancer Research Center - Washington
Proposal: Overcoming mechanisms of resistance to AP-1 engineered CAR-T cell therapy

*The Translational research project that receives one of the highest ratings by the Scientific Advisory Committee is annually designated as the Bob Bast Translational Research Grant. Bob Bast, M.D. chaired the V Foundation’s Scientific Advisory Committee (SAC) for over 20 years and continues to serve on the SAC and Board.
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