• Deming Duan, Keke Wang, Cheng Wei, Dudu Feng, Yonghua Liu, Qingyan He, Xing Xu, Chunling Wang, Shuping Zhao, Leili Lv, Jing Long, Danni Lin, Ai Zhao, Bingmu Fang, Jinhong Jiang, Shixing Tang, and Jimin Gao.
• Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.
• Front Immunol. 2021 Jan 1; 12: 609421.

AbstractChimeric antigen receptor (CAR) technology has revolutionized cancer treatment, particularly in malignant hematological tumors. Currently, the BCMA-targeted second-generation CAR-T cells have showed impressive efficacy in the treatment of refractory/relapsed multiple myeloma (R/R MM), but up to 50% relapse remains to be addressed urgently. Here we constructed the BCMA-targeted fourth-generation CAR-T cells expressing IL-7 and CCL19 (i.e., BCMA-7 × 19 CAR-T cells), and demonstrated that BCMA-7 × 19 CAR-T cells exhibited superior expansion, differentiation, migration and cytotoxicity. Furthermore, we have been carrying out the first-in-human clinical trial for therapy of R/R MM by use of BCMA-7 × 19 CAR-T cells (ClinicalTrials.gov Identifier: NCT03778346), which preliminarily showed promising safety and efficacy in first two enrolled patients. The two patients achieved a CR and VGPR with Grade 1 cytokine release syndrome only 1 month after one dose of CAR-T cell infusion, and the responses lasted more than 12-month. Taken together, BCMA-7 × 19 CAR-T cells were safe and effective against refractory/relapsed multiple myeloma and thus warranted further clinical study.Copyright © 2021 Duan, Wang, Wei, Feng, Liu, He, Xu, Wang, Zhao, Lv, Long, Lin, Zhao, Fang, Jiang, Tang and Gao.

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