Chimeric antigen receptor (CAR) t cells

Abstract

Recent advances in cellular engineering techniques coupled with modern chimeric antigen receptors (CARs) now permit the efficient targeting and killing of malignant cells using patients’ own T cells. Freedom from MHC restriction by relying most commonly on single chain variable fragments of monoclonal antibodies for antigen recognition rather than T cell receptors expands the list of potential targets. Unlike small molecule inhibitors, the targets of CAR T cells are not required to play a critical function in the tumor cell. CAR targets must be extracellular and ideally should have limited expression on normal, vital tissues. By incorporating primary and co-stimulatory domains, CAR T cells possess a substantial proliferative capacity allowing for small cell doses, which reduces the manufacturing burden. This therapeutic approach allows a potent yet customized in vivo response. The potential of CAR T cells to contribute to the overall treatment of cancer is exemplified by the impressive clinical responses with predominantly reversible toxicities seen in early phase clinical trials targeting the B-cell antigen, CD19, in B-lineage hematologic malignancies.