TriBAFF-CAR-T cells eliminate B-cell malignancies with BAFFR-expression and CD19 antigen loss

Li, Guangchao; Zhang, Qing; Liu, Zhi; Shen, Huijuan; Zhu, Yangmin; Zhou, Zhao; Ding, Wen; Han, Siqi; Zhou, Jie; Ou, Ruiming; Luo, Min; Liu, Shuang

BACKGROUND: To investigate the effect of TriBAFF-CAR-T cells on hematological tumor cells. METHODS: TriBAFF-CAR-T and CD19-CAR-T cells were co-cultured with BAFFR-bearing B-cell malignancies at different effector/target ratios to evaluate the anti-tumor effects. In vivo, TriBAFF-CAR-T and CD19-CAR-T cells were intravenously injected into Raji-luciferase xenograft mice. CD19 antigens losing lymphoblasts was simulated by Raji knocking out CD19 (CD19(KO)) to investigate the effect of TriBAFF-CAR-T cells on CD19(KO) Raji. RESULTS: Both TriBAFF-CAR-T and CD19-CAR-T cells significantly induced the lysis of Raji, BALL-1, and Jeko-1. Moreover, when CD19-CAR-T cells specifically caused the lysis of K562 with overexpressed CD19, the lethal effect of TriBAFF-CAR-T cells was also specific for BAFFR-bearing K562 with increasing levels of interleukin-2 and INF-γ. The TriBAFF-CAR-T have the same effect with CD19-CAR-T cells in treating Raji xenofraft mice. TriBAFF-CAR-T cells also have great effect in CD19(KO) Raji cells. CONCLUSIONS: In this study, we successfully constructed novel TriBAFF-CAR-T cells to eliminate BAFFR-bearing and CD19 antigen loss in hematological tumor cells.