Topic: Engineering enhanced CAR-T cell therapy against solid tumors via a synthetic vaccine
Speaker: Assistant Professor MA Leyuan, Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania (UPenn)
Date and time: 13:30–15:00, October 19
Venue: Auditorium, L Building
Host: WANG Haopeng
Abstract:
Chimeric Antigen Receptor T cells (CAR-T) are effective in hematologic malignancies, but strategies to augment their therapeutic impact especially in solid tumors are still needed. Here we demonstrate an approach to enhance CAR-T function by vaccine-boosting donor cells through their chimeric receptor directly in vivo. Amphiphile CAR-T ligand vaccine (amph-vax) were designed, which on injection trafficked to lymph nodes, decorated the surfaces of antigen presenting cells, and primed CAR-T cells in the native lymph node microenvironment. Amph-vax boosting triggered massive CAR-T expansion, increased donor cell polyfunctionality, and enhanced anti-tumor efficacy in multiple immunocompetent tumor models. Unexpectedly, in vivo vaccine boosting of CAR-T cells triggered engagement of the endogenous immune system to circumvent antigen-negative tumor escape and more effectively treat established tumors with pre-existing antigenic heterogeneity. This process was accompanied by shifts in CAR-T metabolism toward oxidative phosphorylation in CAR-T cells and was critically dependent on CAR T-derived IFN-γ. Thus, vaccine boosting provides a clinically-translatable strategy to enhance CAR-T cell therapy against solid tumors. These studies were published in Cell (2023), and Science (2019).
Biography:
01/2022–Current
Assistant Professor, Perelman School of Medicine, University of Pennsylvania
01/2017–12/2021
Postdoctoral Fellow, Howard Hughes Medical Institute
09/2009–12/2016
Ph.D., University of Massachusetts Medical School
09/2004–07/2008
BS, Shandong Normal University