I-Corps: Bioengineered Chimeric Antigen Receptor (CAR) Chips for Screening CAR T-Cell Immunotherapy

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The broader impact/commercial potential of this I-Corps project is the development of Chimeric Antigen Receptor (CAR) T-cell Chip technology to improve the success rate of cancer treatment and shorten the cycle of CAR T-cell immunotherapy, making the entire approach cost-effective and ultimately improving patient welfare. This technology may be especially impactful in low resource communities where current CAR T-cell treatments are unaffordable. Moreover, the CAR-T Chip technology may provide a paradigm shift in drug development: reducing development costs and improving the overall pass rate of newly developed CAR T-cell products in clinical trials. This I-Corps project is based on the development of an improved CAR T-cell therapy with a holistic analysis of the diverse, evolutionary immunosuppressive milieus in the bone marrow and a robust system to probe the interactions between CAR-T cells and the tumor immune microenvironment. Currently, conventional in vitro cell culture and animal models are used to study B-cell acute lymphoblastic lymphoma (B-ALL) pathophysiology and test CAR T-cell functionality. These methods fail to recapitulate the human immune system and thus their clinical full-flanged usage. The new microfluidics-based CAR-T Chip platform may provide a new avenue for screening and improving CAR T-cell therapy by recapitulating patient-specific leukemic bone marrow microenvironment on a chip. The proposed technology may enable a rapid, cost-effective, and high-throughput evaluation of patient-specific response to CAR T-cell immunotherapy, as well as alternative treatments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.