The T cells of our immune system have a “license to kill” and can be genetically reprogrammed to attack cancer cells. These so-called Chimeric Antigen Receptor (CAR) T cells have proven effective in the clinic against multiple tumor types. However, CAR T cells can undergo exhaustion and die over time. The short-term survival of these cells is one of the main reasons for therapeutic failure in a significant fraction of patients.
Current efforts to prolong the persistence of CAR T cells rely on drugs or genetic modifications that prevent their exhaustion. While such strategies might yield more durable cells, they might also unleash their uncontrolled proliferation, with the risks of toxicity and oncogenic transformation. In contrast, to ensure the durability of our physiological immune responses Nature relies on a limited population of long-lived, dormant Stem cells able to give rise to both other Stem cells and active, short-lived Effector cells. The overall Dr. Migliara’s project aims to apply this natural principle to CAR T cells and design more durable, yet safe anti-cancer immunotherapies.
Projects and Grants
Nature-inspired immune cell engineering toward durable anti-cancer therapies
University of California, San Francisco | All Cancers | 2023 | Wendell Lim, PhD
