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

转基因编码的截短型人类表皮生长因子受体,用于消除抗 B 细胞成熟抗原 CAR-T 细胞

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作者:Qingming Wang, Feng He, Wenfeng He, Yan Huang, Junquan Zeng, Fuming Zi, Jifu Zheng, Yan Fei, Jing Xu, Yuan Song, Xiaoyin Ye, Ruomei Lai, Longlong Ye, Bo Zhu

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.

Conclusions

We confirm that BCMA is a suitable target for CAR- T cells and tEGFR is a effective tool for cellular 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.

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