Federal Grant Award Summary

The National Cancer Institute awarded Weill Medical College of Cornell University a Project Grant totaling $716,183.00 (awarded May 13, 2026; completion April 30, 2031) under the Cancer Treatment Research program (CFDA 93.395) to investigate chimeric antigen receptor (CAR) T-cell therapies and develop enhanced immunotherapeutic approaches for cancer treatment. The research focuses on interrogating co-inhibitory and co-stimulatory molecules that limit CAR-T cell efficacy, specifically examining how programmed death ligand 1 (PD-L1) expression—both intrinsic to T cells and acquired from tumor cells through trogocytosis—suppresses CAR-T activity. The project will also evaluate the therapeutic potential of 80BB, a novel synthetic dual-costimulatory receptor that combines CD80 binding capability with enhanced signaling through the 4-1BB endodomain while functioning as a CTLA-4 switch receptor.

The deliverables encompass three primary research aims: determining mechanisms by which intrinsic PD-L1 regulates CAR-T function under varying antigen stimulation conditions; defining the functional impact of tumor-derived PD-L1 transfer on CAR-T performance using in vitro assays and in vivo leukemia and melanoma models; and establishing mechanisms of action and therapeutic efficacy of the engineered 80BB-based platform designed to overcome PD-L1-mediated suppression while preserving beneficial CD28 and CTLA-4 interactions. The research addresses critical challenges in adoptive cell therapy by investigating resistance mechanisms and developing targeted interventions to improve treatment outcomes across diverse CAR-T platforms.