Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Department of Oncology, Xinqiao Hospital, The Army Medical Unviersity, Chongqing, China; Shanghai Hrain Biotechnology Co., Ltd, Shanghai, China.
Cell Immunol. 2021 May;363:104342. doi: 10.1016/j.cellimm.2021.104342. Epub 2021 Mar 14.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: We confirm that BCMA is a suitable target for CAR- T cells and tEGFR is a effective tool for cellular ablation.
背景：嵌合抗原受体 T 细胞（CAR-T）针对 B 细胞成熟抗原（BCMA）已被用于治疗多发性骨髓瘤（MM）。共表达截断型人表皮生长因子受体（tEGFR）的 CAR-T 细胞已被提议用于体内细胞消融。
方法：我们设计并测试了一种新型的抗 BCMA CAR。我们使用逆转录病毒载体转导 T 细胞，使其表达 CAR 和 tEGFR。我们评估了抗 BCMA-CAR 转导的 T 细胞的功能，包括细胞因子产生、增殖、细胞毒性和体内 BCMA 肿瘤的清除。西妥昔单抗用于体内细胞消融。
结果：CAR-T 细胞可以特异性识别 BCMA，并且抗 BCMA CAR-T 细胞可以特异性地产生由 BCMA 诱导的干扰素-γ和细胞毒性，并在体内清除肿瘤。西妥昔单抗可以介导抗体依赖性细胞毒性和体内消除。
结论：我们证实 BCMA 是 CAR-T 细胞的合适靶标，tEGFR 是细胞消融的有效工具。
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