PRESENTED BY
Leyuan Ma, Ph.D.
Postdoctoral Fellow
Immune Engineering and Cancer Immunotherapy
Howard Hughes Medical Institute
Massachusetts Institute of Technology
 

ABSTRACT
Chimeric antigen receptor (CAR) T-cell therapy has shown dramatic clinical responses in hematologic malignancies, with a high proportion of durable complete remissions elicited in leukemia and lymphomas. However, achieving the full promise of CAR T-cell therapy, especially in solid tumors, will require further advances in this form of cellular therapy. A key challenge is maintaining a sufficient pool of functional CAR T cells in vivo. We recently developed a strategy to target vaccines to lymph nodes, by linking peptide antigens to albumin-binding phospholipid-polymers. Constitutive trafficking of albumin from blood
to lymph makes it ideal chaperone to concentrate these “amphiphile-vaccine” molecules in lymph nodes that would otherwise be rapidly dispersed in the bloodstream following parenteral injection. These lipid-polymer conjugates also exhibit the property that they insert in cell membranes on arrival in lymph nodes. Here, we generated amphiphile CAR T ligand (amph-ligand) vaccine by exploiting these dual lymph node targeting and membrane-decorating properties to repeatedly expand and rejuvenate CAR T cells through the chimeric receptor in native lymph node microenvironment. We evaluated this approach in the presence of a complete host immune system. Amph-ligand vaccine boosting triggered massive CAR T expansion, increased donor cell polyfunctionality, and enhanced anti-tumor efficacy in multiple immunocompetent tumor models. We demonstrate two approaches to generalize this strategy to any CAR, enabling this simple MHC-independent vaccination
approach to enhance CAR T functionality to be applied to existing CAR T cell designs. Taken together, our amph-ligand vaccine provides a simple engineering solution to augment CAR T-cell therapy.

 
BIOGRAPHY
Dr. Leyuan Ma, Ph.D. is currently a Postdoctoral Research Fellow at Howard Hughes Medical Institute (HHMI) and Massachusetts Institute of Technology. He previously obtained his Ph.D. in Molecular, Cell and Cancer Biology from HHMI and the University of Massachusetts Medical School and his B.S. in Biosciences and Bioengineering from Shandong Normal University in China.