Genetically modified cells, such as CAR T cells, are highly potent “living drugs” that have provided remarkable benefits for some patients with leukemia and lymphoma. Unfortunately, current cell-based treatments aren’t yet effective against solid cancers, in part because there often isn’t a single molecular marker that can distinguish the mutated cells from the normal, healthy cells surrounding them. To overcome this challenge, Dr. Piraner is working to improve the capabilities of CAR T therapy with an additional layer of control using an engineered receptor known as SynNotch.
By enabling the CAR T cells to sense other factors in the environment and ensuring they only attack once they’ve recognized a second cancer-associated signal, SynNotch receptors have the potential to significantly improve the safety and effectiveness of these promising therapies. Dr. Piraner is working to optimize these proteins for clinical applications by introducing novel components into the SynNotch receptor architecture. These new pieces will let scientists more precisely control the dynamics of T cell activation, enabling SynNotch-equipped T cells to activate only under a defined set of conditions that are matched to those of solid tumors. This technology will enable T cells to more aggressively attack cancer cells while minimizing off-target side effects on healthy tissues.
Projects and Grants
Engineered human-compatible surface receptors for precise control of next-gen cell-based therapeutics
University of California, San Francisco | All Cancers | 2020 | Kole T. Roybal, Ph.D.
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