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

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

doi:10.1186/s12935-021-01923-x

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

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

Authors

Guangchao Li^#^{1

2}, Qing Zhang^#¹, Zhi Liu^#¹, Huijuan Shen¹, Yangmin Zhu¹, Zhao Zhou², Wen Ding², Siqi Han³, Jie Zhou⁴, Ruiming Ou^{5

6}, Min Luo^{7

8

9}, Shuang Liu^{10

11}

Affiliations

¹ Department of Hematology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong Province, 510317, China.
² Guangzhou Bio-gene Technology Co., Ltd, Guangzhou, Guangdong Province, 510530, China.
³ Department of Medical Oncology, Jinling Hospital, Nanjing Clinical School of Southern Medical University, Nanjing, Jiangsu Province, 210002, China.
⁴ Department of Hematology, People's Hospital of Deyang City, Deyang, Sichuan Province, 618000, China.
⁵ Department of Hematology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong Province, 510317, China. Ouruiming@126.com.
⁶ Department of Hematology, Guangdong Second Provincial General Hospital, Xin Gang Zhong Road 466#, Haizhu Distict, Guangzhou, Guangdong Province, 510317, China. Ouruiming@126.com.
⁷ Department of Hematology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong Province, 510317, China. mluo@gzbiogene.com.
⁸ Guangzhou Bio-gene Technology Co., Ltd, Guangzhou, Guangdong Province, 510530, China. mluo@gzbiogene.com.
⁹ Department of Hematology, Guangdong Second Provincial General Hospital, Xin Gang Zhong Road 466#, Haizhu Distict, Guangzhou, Guangdong Province, 510317, China. mluo@gzbiogene.com.
¹⁰ Department of Hematology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong Province, 510317, China. Liush@gd2h.org.cn.
¹¹ Department of Hematology, Guangdong Second Provincial General Hospital, Xin Gang Zhong Road 466#, Haizhu Distict, Guangzhou, Guangdong Province, 510317, China. Liush@gd2h.org.cn.

^# Contributed equally.

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 (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.

Keywords: BAFF; CAR-T; Hematological tumor; Trimer; Tumor relapse.

Abstract

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