Events Calendar

Title: "Development of a Tunable Protein Release Hydrogel for Enhancing CAR T cell Activity"

Advisory Committee: Timothy O'Shea, PhD – BU BME (Chair) Mark Grinstaff, PhD – BU BME (Co-Advisor) Wilson Wong, PhD – BU BME (Co-Advisor) David Sherr, PhD – BU School of Public Health & Environmental Health

Abstract: Chimeric antigen receptor (CAR) T cells are genetically engineered T lymphocytes designed to sense antigens and mount an immune response. Though CAR T cells have received FDA approval for the treatment of several hematologic malignancies, success in solid tumors is limited by a lack of specific antigens, the immunosuppressive tumor microenvironment, and treatment-limiting adverse effects such as on-target, off-tumor toxicity and cytokine release syndrome. Though investigators report strategies for mitigating these limitations such as biomaterials for reshaping the tumor microenvironment, and logic-gated CAR T cells to prevent non-specific toxicity, no proposed strategy has overcome each of these barriers. To surmount these limitations, I propose the use of a novel self-assembled hydrogel for implantation into the tumor. This hydrogel will be used in conjunction with a split CAR T cell called a zipCAR, which uses a split adaptor protein (zipFv) to sense antigens. The hydrogel supplies the zipFv adaptor protein, cytokines (IL-7), and chemokines (CXCL9). I hypothesize that the use of this in situ hydrogel will overcome the barriers to CAR T cell therapy in solid tumors by: (1) opposing T cell anergy and promoting proliferation in the resection cavity, (2) preventing antigen escape via encapsulation of zipFvs targeting multiple antigens, and (3) imparting spatiotemporal control over CAR T cell activity.