4.5 Article

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

Journal

CELLULAR IMMUNOLOGY
Volume 363, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2021.104342

Keywords

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

Funding

  1. Jiangxi Key Research and Development Program of China [20201BBG71009, 20171BBG70057]
  2. Shanghai HRAIN Biotechnology Co., Ltd.

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The study confirmed that CAR-T cells targeting BCMA can effectively eliminate multiple myeloma, and CAR-T cells co-expressing tEGFR have the potential for cellular ablation.
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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