Rapid generation of CD19 CAR-T cells by minicircle DNA enables anti-tumor activity and prevents fatal CAR-B leukemia

Cancer Lett. 2023 Aug 1:568:216278. doi: 10.1016/j.canlet.2023.216278. Epub 2023 Jun 22.

Abstract

Manufacturing chimeric antigen receptor (CAR)-T cells using viral vectors is expensive and time-consuming. In addition, during viral transduction, genes encoding CARs are randomly integrated into the genome, which can cause oncogenesis or produce devastating CAR-tumor cells. Here, using a virus-free and non-transgenic minicircle DNA (mcDNA) vector, we enabled the rapid generation of CD19 CAR-T cells within two days. Furthermore, we demonstrated in vitro and in xenograft models that the antitumor effects of CD19 CAR-T cells produced by mcDNA are as effective as those produced by viral vectors. Finally, we showed that our manufacturing process avoids the production of fatal CAR-tumor cells. Taken together, we have provided a fast, effective, and therapeutically safe method for generating CD19 CAR-T cells for the treatment of leukemia.

Keywords: CD19; Chimeric antigen receptor; Leukemia; Minicircle DNA; T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA
  • Humans
  • Immunotherapy, Adoptive / methods
  • Leukemia* / genetics
  • Leukemia* / therapy
  • Neoplasms*
  • Receptors, Antigen, T-Cell / genetics
  • T-Lymphocytes

Substances

  • Receptors, Antigen, T-Cell
  • DNA