CAR-modified T-cell therapy for cancer: an updated review

Abstract

The use of chimeric antigen receptor (CAR)-modified T cells is a promising approach for cancer immunotherapy. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in T-cell activation subsequent to antigen binding. Optimal tumor removal through CAR-modified T cells requires suitable target antigen selection, co-stimulatory signaling domain, and the ability of CAR T cells to traffic, persist, and retain antitumor function after adoptive transfer. There are several elements which can improve antitumor function of CAR T cells, including signaling, conditioning chemotherapy and irradiation, tumor burden of the disease, T-cell phenotype, and supplementary cytokine usage. This review outlines four generations of CAR. The pre-clinical and clinical studies showed that this technique has a great potential for treatment of solid and hematological malignancies. The main purpose of the current review is to focus on the pre-clinical and clinical developments of CAR-based immunotherapy.