4SCAR2.0: a multi-CAR-T therapy regimen for the treatment of relapsed/refractory B cell lymphomas

Chimeric antigen receptor (CAR) gene therapy is a breakthrough technology in treating refractory hematologic malignancies 1 , 2 , 3 . CD19 CAR-T therapy has emerged as a promising treatment for the management of B cell malignancies. However, malignant cell populations of leukemia or lymphoma are highly heterogeneous and tend to diverse into CD19-negative cells after targeted treatment. Antigen escape leading to disease recurrence is the major reason for the failure of currently approved CAR-T cell therapies 4 . Similar to combining different chemotherapy agents in order to overcome chemotherapy resistance, investigators have started combining CAR-T cells targeting different antigens, in order to overcome tumor antigen escape 5 , 6 . Besides, the associated severe adverse effects, the exhaustion of CAR-T cells in vivo, and the high cost of individualized CAR-T cell preparation are major limitations to the current CAR technology 7 .