TCR/Chimeric Antigen Receptor (CAR) Cross-Antagonism to Fine-Tune CAR-T cell Immunotherapy

Abstract Chimeric antigen receptor (CAR) T cells, are created by extracting cells from a cancer patient, engineering them to express CAR targeting tumor specific molecule, then reintroducing back into the patient. A patient’s contain their own endogenous cell receptors (TCRs) however, which could potentially interact with exogenous inserted cell. In this study, we examine how TCR and signals upon CAR-T activation. We show that weak stimulation can reduce (antagonize) or increase overall response, both in vitro vivo, across multiple models, mouse human cells. further behavior of these TCR/CAR interactions be manipulated changing various characteristics TCR, CAR, associated ligands. While is complex, it described single mathematical model based on adaptive kinetic proofreading scheme ligand discrimination. conclude presenting potential applications for immunotherapy. Intramural Research Program National Cancer Institute