Targeting BCMA in multiple myeloma using chimeric antigen receptor-engineered T cells
10.3760/cma.j.issn.0253-2727.2019.10.002
- VernacularTitle: 靶向BCMA的嵌合抗原受体T细胞抗多发性骨髓瘤作用研究
- Author:
Mengjun ZHONG
1
,
2
,
3
;
Yingxi XU
;
Haiyan XING
;
Kejing TANG
;
Zheng TIAN
;
Qing RAO
;
Min WANG
;
Jianxiang WANG
Author Information
1. Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
2. State Key Laboratory of Experimental Hematology
3. National Clinical Research Center for Blood Diseases, Tianjin 300020, China
- Publication Type:Journal Article
- Keywords:
Multiple myeloma;
Chimeric antigen receptor;
B-cell maturation antigen;
Immunotherapy
- From:
Chinese Journal of Hematology
2019;40(10):804-811
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To construct the BCMA-CAR using the B-cell maturation antigen (BCMA) specific ligand APRIL as antigen binding region and to validate the effect of BCMA-CAR modified T cells (BCMA-CAR-T) on myeloma cells.
Methods:The BCMA-CAR was constructed using the BCMA specific ligand APRIL as antigen binding domain and 4-1BB as the costimulatory domain. The specific cytotoxicity against BCMA+ myeloma cell lines and primary multiple myeloma (MM) cells in vitro were evaluated. In addition, BCMA+ myeloma xenograft mouse model was established to assess the anti-tumor effect of BCMA-CAR-T cell therapy in vivo.
Results:BCMA-CAR-T cells could specifically kill BCMA+ myeloma cell lines (For BCMA-CAR-T cells, BCMA+ cells are almost undetectable in the E∶T ratio of 1∶4) and MM patients’ bone marrow mononuclear cells (the proportion of residual cells in BCMA-CAR-T and vector-T groups was 16.0% vs 66.85%, P=0.003) with significant degranulation (CAR-T and vector-T cells cocultured with MM1.S, H929 and U266 had degranulation levels of 33.30% vs 5.62%, 16.97% vs 2.95% and 25.87% vs 2.97%, respectively, P<0.001) and cytokines release (P<0.01) in vitro. In a human BCMA+ myeloma xenograft mouse model, BCMA-CAR-T cells could significantly prolong the survival of mice (The median survival time of mice treated with BCMA-CAR-T and vector-T cells was 87.5 days and 67.5 days, respectively, P<0.001) .
Conclusion:The ligand-based BCMA-CAR-T cells could be a promising strategy for BCMA+ multiple myeloma treatment.
