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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • B-Cell Maturation Antigen / immunology*
  • B-Cell Maturation Antigen / metabolism
  • Cell Line, Tumor
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Female
  • HEK293 Cells
  • Heterografts
  • Humans
  • Immunotherapy, Adoptive / methods*
  • K562 Cells
  • Male
  • Mice
  • Mice, Inbred NOD
  • Middle Aged
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Receptors, Chimeric Antigen / immunology
  • T-Lymphocytes / immunology
  • Transgenes
  • Xenograft Model Antitumor Assays

Substances

  • B-Cell Maturation Antigen
  • Receptors, Chimeric Antigen
  • ErbB Receptors