CAR-T Cell Research

A therapeutic CAR (chimeric antigen receptor) is a transmembrane protein designed with an extracellular domain based on an antibody single-chain variable fragment (scFv) and intracellular signaling domains derived from the TCR g chain, along with other costimulatory receptors. The scFv provides a specific binding domain that recognizes target proteins on cancer cells. A patient’s own T cells are isolated and activated, then transfected with a gene expressing the CAR. This reprograms the T cells to identify and attack tumor cells expressing the target protein, creating personalized immune cells designed to specifically target the patient’s cancer.

The first FDA approved treatments were CAR-T cells directed against the B cell protein CD19. Success with CD19 has inspired new research identifying additional targets for several blood cancers and even solid tumors. For example, early clinical trials using CAR-T treatment suggest BCMA and CD22 are promising targets for multiple myeloma and acute lymphoblastic leukemia. CD19-targeting CAR-T cells are also in development as co-therapies with therapeutic antibodies targeting the PD-1:PD-L1 and CD28:CTLA4 pathways. The aim of these early studies is to determine if CAR-T cells can overcome the challenges of adaptive resistance to immune checkpoint therapies.