CELLULAR THERAPIES

Adoptive T cell Therapy is a rapidly growing field and its recent clinical successes have significantly shaped the current field of immune-oncology. Several modalities have been explored, including expansion and re-infusion of tumor-infiltrating T cells, expansion of tumor antigen-specific T cells from peripheral blood, and infusion of genetically modified T cells (e.g. chimeric antigen receptor (CAR) T cells, transgenic TCR). These approaches have shown remarkable efficacy in hematologic malignancies including B-ALL and more recently Multiple Myeloma, but have been with limited success in solid tumors.

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The major limitations hindering efficacy in the solid tumor setting include limited function and persistence of the adoptively transferred T cells by activation of negative regulators and induction of T cell exhaustion through the hostile tumor-microenvironment.
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The Kean lab is now addressing these limitations by interrogation of different complementary strategies. Using CRIPSR Cas9 technology we are deleting negative regulators of T cell activation and persistence to increase function and long-term survival of T cells after adoptive transfer. We have established a multitude of in vitro and in vivo tumor targeting T cell models, to validate our strategies and are additionally using single cell transcriptomic and epigenetic assays to explore underlying mechanisms. We are also utilizing our established non-human primate CD20 CAR T cell model to further assess function, persistence and toxicity of our genetically modified T-cells and provide the rationale for future clinical translation.