Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.609421
Keywords
multiple myeloma; CAR-T; BCMA; IL-7; CCL19
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Funding
- Scientific Research Fund of National Health Commission of PR China [WKJ-ZJ-1928]
- Guangdong Provincial Natural Science Foundation [2019A1515110831]
- Wenzhou Municipal Science and Technology Research Program [ZS2017014, 2018ZY001]
- Lishui Municipal Science and Technology Research Program [2019ZDYF19]
- Zhejiang Provincial Major Research Project
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BCMA-7 x 19 CAR-T cells have shown superior efficacy and safety in treating refractory/relapsed multiple myeloma, making them a promising therapeutic option that warrants further clinical studies.
Chimeric 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 x 19 CAR-T cells), and demonstrated that BCMA-7 x 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 x 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 x 19 CAR-T cells were safe and effective against refractory/relapsed multiple myeloma and thus warranted further clinical study.
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