• M J Zhong, Y X Xu, H Y Xing, K J Tang, Z Tian, Q Rao, M Wang, and J X Wang.
• Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; State Key Laboratory of Experimental Hematology; National Clinical Research Center for Blood Diseases, Tianjin 300020, China.
• Zhonghua Xue Ye Xue Za Zhi. 2019 Oct 14; 40 (10): 804-811.

AbstractObjective: 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.

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