A transgene-encoded truncated human epidermal growth factor receptor for depletion of anti- B-cell maturation antigen CAR-T cells

• Published in: Cellular immunology Vol. 363; p. 104342
• Main Authors: Wang, Qingming, He, Feng, He, Wenfeng, Huang, Yan, Zeng, Junquan, Zi, Fuming, Zheng, Jifu, Fei, Yan, Xu, Jing, Song, Yuan, Ye, Xiaoyin, Lai, Ruomei, Ye, Longlong, Zhu, Bo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.05.2021
• Subjects: Adoptive T cell therapy; B-cell maturation antigen; Chimeric antigen receptor; Multiple myeloma; Chimeric antigen receptor; Adoptive T cell therapy; B-cell maturation antigen; Multiple myeloma
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2021.104342

•BCMA is a suitable and promising target for CAR- T therapy. Anti-BCMA CAR-T cells could exhibit interferon-γ and cytotoxicity and eradicate tumor in vivo.•We developed a novel “safety switch” CAR-T to dampen CAR-T cells by using a commercially available drug as a safety mechanism in the event of an adverse reaction in patients.•This new development could make it possible to engineer a safer CAR-T and offer virtually unlimited potential for cancer therapy. Chimeric antigen receptor T cells (CAR-T) against B-cell maturation antigen (BCMA) has been used to treat multiple myeloma (MM). CAR-T cells co-expressing a truncated human EGFR (tEGFR) has been proposed for in vivo cell ablation. We designed and tested a novel anti-BCMA CAR. We transduced T cells with retroviral vectors encoding CAR and tEGFR. The anti-BCMA-CAR-transduced T cells were evaluated for the functions including cytokine production, proliferation, cytotoxicity, and in vivo tumor eradication of BCMA. Cetuximab was used for in vivo cell ablation. The CAR-T cells could specifically recognize BCMA, and anti-BCMA CAR-T cells could exhibit interferon-γ and cytotoxicity specifically produced by BCMA and eradicate tumor in vivo. Cetuximab could mediate antibody-dependent cellular cytotoxicity and in vivo elimination. We confirm that BCMA is a suitable target for CAR- T cells and tEGFR is a effective tool for cellular ablation.