NextGen CARs: the race is on

In this issue of Blood, Tong et al present the preclinical and clinical development of an optimized, bivalent tandem CD20/CD19 chimeric antigen receptor (CAR) construct (see figure). Preclinically, they demonstrated dual-antigen specificity, enhanced immune synapse formation, and superior antitumor activity in vitro and in vivo in a murine xenograft model compared with alternative constructs generated from the same 2 single-chain variable fragment (scFv) regions derived from Leu-16 (anti-CD20) and FMC63 (anti-CD19) murine monoclonal antibodies. Next, they performed a phase 1/2a clinical trial of this construct in patients with relapsed or refractory mature B-cell lymphomas or chronic lymphocytic leukemia.(1) Their observations suggest that a single chimeric receptor targeting 2 separate tumor antigens is a safe and potentially effective CAR T-cell approach with potential to prevent therapeutic failure due to single antigen loss by tumor cells after CD19-directed therapies as well as to enhance the functional activity of the CAR in T cells.