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

Author:

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

Abstract

Abstract 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 (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.

Funder

Guangzhou Science and Technology Plan Project

Foundation of Guangdong Second Provincial General Hospital

Doctoral Workstation Foundation of Guangdong Second Provincial General Hospital

Guangdong Medical Scientific Research

Pearl River S&T Nova Program of Guangzhou from Guangzhou Municipal Science and Technology Bureau

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Genetics,Oncology

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