Functional Validation of the RQR8 Suicide /Marker Gene in CD19 CAR-T Cells and CLL1CAR-T Cells

Ann Hematol. 2023 Jun;102(6):1523-1535. doi: 10.1007/s00277-023-05227-0. Epub 2023 Apr 22.

Abstract

Chimeric antigen receptor T cell therapy (CAR-T) is a novel treatment that has produced unprecedented clinical effects in patients with hematological malignancies. Acute adverse events often occur following adoptive immunotherapy. Therefore, a suicide gene is helpful, which is a genetically encoded mechanism that allows selective destruction of adoptively transferred T cells in the face of unacceptable toxicity. RQR8 is a gene that integrates CD34 and CD20 epitopes. In our study, we incorporated the suicide gene RQR8 into CAR-T cells, so it enabled rituximab to eliminate vector/transgene-expressing T cells via antibody-dependent cell-mediated cytotoxicity and complement dependent cytotoxicity. In this work, we explored the functionality of RQR8 CAR-T cells in vitro and in vivo. We believe that RQR8 as a safety switch will make CAR-T cell therapy safer and less costly.

Keywords: Antibody-dependent cell-mediated cytotoxicity; Chimeric antigen receptor T cells; Complement-dependent cytotoxicity; Marker/suicide gene; Rituximab.

MeSH terms

  • Antigens, CD19 / genetics
  • Apoptosis
  • Humans
  • Immunotherapy, Adoptive
  • Receptors, Chimeric Antigen* / genetics
  • Rituximab
  • T-Lymphocytes*

Substances

  • Receptors, Chimeric Antigen
  • Rituximab
  • Antigens, CD19