A Transgene-Encoded Truncated Human Epidermal Growth Factor Receptor For Depletion Of Anti- B-Cell Maturation Antigen Car-T Cells

CELLULAR IMMUNOLOGY(2021)

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摘要
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? 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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关键词
Multiple myeloma, Chimeric antigen receptor, Adoptive T cell therapy, B-cell maturation antigen
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