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.
Guangchao Li  #  1  2 ,  Qing Zhang  #  1 ,  Zhi Liu  #  1 ,  Huijuan Shen  1 ,  Yangmin Zhu  1 ,  Zhao Zhou  2 ,  Wen Ding  2 ,  Siqi Han  3 ,  Jie Zhou  4 ,  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. [email protected].
  • 6. Department of Hematology, Guangdong Second Provincial General Hospital, Xin Gang Zhong Road 466#, Haizhu Distict, Guangzhou, Guangdong Province, 510317, China. [email protected].
  • 7. Department of Hematology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong Province, 510317, China. [email protected].
  • 8. Guangzhou Bio-gene Technology Co., Ltd, Guangzhou, Guangdong Province, 510530, China. [email protected].
  • 9. Department of Hematology, Guangdong Second Provincial General Hospital, Xin Gang Zhong Road 466#, Haizhu Distict, Guangzhou, Guangdong Province, 510317, China. [email protected].
  • 10. Department of Hematology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong Province, 510317, China. [email protected].
  • 11. Department of Hematology, Guangdong Second Provincial General Hospital, Xin Gang Zhong Road 466#, Haizhu Distict, Guangzhou, Guangdong Province, 510317, China. [email protected].
  • # Contributed equally.
PMID: 33865370 DOI: 10.1186/s12935-021-01923-x
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.

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