Tandem CAR and single CAR T cells have different fates and therapeutic potency

Chimeric antigen receptor T (CAR T) cells targeting CD19 have achieved breakthroughs in the treatment of haematological malignancies, but many clinical studies have also shown that a proportion of patients relapse after remission. In this study, we designed a series of tandem CARs (TanCARs) and found that TanCAR7 T cells retained relatively potent antitumour activity compared with single CAR T cell upon target antigen recognition. It may be associated with stable immunological synapse formation and rapid degranulation. Our transcriptional analysis underscores the potential of scFv domains binding to direct different T cell fates. In order to assess the different phenotypic and functional patterns of CARs between TanCAR7 and single CAR, we compared the genome-wide transcriptional profiles of TanCAR7, CD19 CAR and CD20 CAR T cell after cocultured with Raji cells for 24 h.