Adoptive T-cell therapy of B-cell malignancies: conventional and physiological chimeric antigen receptors

Hematological malignancies remain incurable diseases because of the high risk of relapse, even after complete remission. Adoptive T-cell therapy (ACT) using modified T cells with chimeric antigen receptors (CARs) targeted to specific tumor-associated antigens expressed by B-cell malignancies represents an attractive approach for cancer immunotherapy. Investigators optimized the design of CARs to enhance receptor mediated T cell signaling and demonstrated that second and third generation CARs, including various costimulatory molecules, resulted in enhanced T-cell persistence and sustained antitumor activity in both in vitro and in vivo mouse models as well as clinical trials. We highlight advances in the use of CARs in the treatment of B-cell malignancies and future challenges in the use of adoptive therapy with CAR-engineered T cells.