A transgene-encoded truncated human epidermal growth factor receptor for depletion of anti- B-cell maturation antigen CAR-T cells
Qingming Wang, Feng He, Wenfeng He, Yan Huang, Junquan Zeng, Fuming Zi, Jifu Zheng, Yan Fei, Jing Xu, Yuan Song, Xiaoyin Ye, R Q Lai, Long-Long Ye, Bo Zhu
Abstract
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.