CAR-T cells inflict sequential killing of multiple tumor target cells

Abstract

Adoptive therapy with chimeric antigen receptor (CAR) T cells shows great promise clinically. However, there are important aspects of CAR-T-cell biology that have not been explored, particularly with respect to the kinetics of activation, immune synapse formation, and tumor cell killing. Moreover, the effects of signaling via the endogenous T-cell receptor (TCR) or CAR on killing kinetics are unclear. To address these issues, we developed a novel transgenic mouse (designated CAR.OT-I), in which CD8+ T cells coexpressed the clonogenic OT-I TCR, recognizing the H-2K-presented ovalbumin peptide SIINFEKL, and an scFv specific for human HER2. Primed CAR. OT-I Tcells were mixed with SIINFEKL-pulse..