Investigating a Novel Inhibitory Receptor in Regulating CAR-T Cell Persistence and Function

ABSTRACT Chimeric antigen receptor (CAR)-engineered T cell therapy is a breakthrough immunotherapy for lymphoma. Nevertheless, 40-60% of responding patients relapse, in part due to the poor persistence of CAR-T cells. In this regard, our preliminary studies have identified the role of an inhibitory receptor that functions to restrict the

expansion and persistence of T cells. This proposal will test the hypothesis that similar to natural T cells, CAR- T cells were also controlled by this inhibitory axis: in Aim 1, we will examine the causal role of this receptor axis in impairing the therapeutic efficacy of murine CAR-T cells. In Aim 2, we will examine the expression of this

inhibitory receptor in human CAR-T cells and test effects of blocking this receptor in augmenting CAR-T function. Together, these studies will guide future studies to develop potent therapeutics for improving the clinical efficacies of CAR-T therapies.