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

TriBAFF-CAR-T 细胞通过 BAFFR 表达和 CD19 抗原丢失消除 B 细胞恶性肿瘤

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

Background

To investigate the effect of TriBAFF-CAR-T cells on hematological tumor 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.

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 (CD19KO) to investigate the effect of TriBAFF-CAR-T cells on CD19KO 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 CD19KO 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.

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