三价BAFF嵌合抗原受体T细胞可消除表达BAFFR且丧失CD19抗原的B细胞恶性肿瘤。

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

作者信息

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

机构信息

Department of Hematology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong Province, 510317, China.

Guangzhou Bio-gene Technology Co., Ltd, Guangzhou, Guangdong Province, 510530, China.

出版信息

Cancer Cell Int. 2021 Apr 17;21(1):223. doi: 10.1186/s12935-021-01923-x.

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) to investigate the effect of TriBAFF-CAR-T cells on CD19 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 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.

背景

研究三价B细胞活化因子嵌合抗原受体T细胞（TriBAFF-CAR-T细胞）对血液肿瘤细胞的作用。

方法

将TriBAFF-CAR-T细胞和CD19-CAR-T细胞与表达B细胞活化因子受体（BAFFR）的B细胞恶性肿瘤细胞以不同的效应细胞/靶细胞比例共培养，以评估抗肿瘤效果。在体内，将TriBAFF-CAR-T细胞和CD19-CAR-T细胞静脉注射到Raji荧光素酶异种移植小鼠体内。通过Raji敲除CD19（CD19-）模拟CD19抗原缺失的淋巴母细胞，以研究TriBAFF-CAR-T细胞对CD19-Raji的作用。

结果

TriBAFF-CAR-T细胞和CD19-CAR-T细胞均能显著诱导Raji、BALL-1和Jeko-1细胞的裂解。此外，当CD19-CAR-T细胞特异性导致过表达CD19的K562细胞裂解时，TriBAFF-CAR-T细胞的杀伤作用也对表达BAFFR的K562细胞具有特异性，且白细胞介素-2和干扰素-γ水平升高。TriBAFF-CAR-T细胞在治疗Raji异种移植小鼠方面与CD19-CAR-T细胞具有相同的效果。TriBAFF-CAR-T细胞对CD19-Raji细胞也有显著作用。