Project Grant R01AI201579

The National Institute of Allergy and Infectious Diseases awarded Purdue University $498,154 on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to fund research into signaling mechanisms governing chimeric antigen receptor T cell activation.

The research addresses a critical gap in understanding how CAR T cells recognize and eliminate target cells while avoiding off-target activation and collateral damage. CAR T cells express artificial receptors that bind target antigens and direct cytotoxic vesicles toward target cells for destruction, but toxicities observed in clinical use suggest incomplete understanding of activation mechanisms. The five-year project builds on the recipient's recent discovery that CAR T cells display single-molecule, single-cell sensitivity resembling native T cell receptor activity. The research team predicts that interactions between the native T cell receptor and the engineered CAR are critical for CAR T cell potency and have been previously overlooked. The work measures T cell receptor and CAR interactions at the cell surface (Aim 1) and proximal kinase-mediated signaling interplay (Aim 2) controlling CAR T cell activation. The project leverages an in vitro reconstitution platform that captures the binding history experienced by individual immune cells and correlates these inputs to cell-wide outcomes including polarization and degranulation.

Performance occurs at West Lafayette, Indiana. The period of performance runs through August 31, 2031. This is a Project Grant, the standard assistance type under the NIAID research program.