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. 2021 May:363:104342.
doi: 10.1016/j.cellimm.2021.104342. Epub 2021 Mar 14.

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

Qingming Wang  1 , Feng He  2 , Wenfeng He  3 , Yan Huang  4 , Junquan Zeng  5 , Fuming Zi  6 , Jifu Zheng  6 , Yan Fei  6 , Jing Xu  6 , Yuan Song  6 , Xiaoyin Ye  7 , Ruomei Lai  8 , Longlong Ye  6 , Bo Zhu  9
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Free article

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

Qingming Wang et al. Cell Immunol. 2021 May.
Free article

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.

Keywords: Adoptive T cell therapy; B-cell maturation antigen; Chimeric antigen receptor; Multiple myeloma.

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