IL-24 improves efficacy of CAR-T cell therapy by targeting stemness of tumor cells

Br J Cancer. 2024 May;130(8):1337-1347. doi: 10.1038/s41416-024-02601-1. Epub 2024 Feb 12.

Abstract

Background: Cancer stem cells (CSCs) induce therapeutic resistance and may be an important barrier to cancer immunotherapy. Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable efficacy in clinical settings. However, CAR-T cell therapy fails in a large proportion of patients, especially in those with solid tumors. It is unclear how CSCs mediate resistance to CAR-T cells, and whether CAR-T cells can more effectively eradicate CSCs.

Methods: In this study, the effect of CSCs on CAR-T cell therapy was determined using in vitro and in vivo assays. Subsequently, Interleukin-24 (IL-24) was expressed along with CAR in T cells. Further in vitro and in vivo tests were performed to determine the effects of IL-24 on CSCs and CAR-T cell therapy.

Results: IL-24 induced apoptosis in CSCs and contributed to T cell activation, differentiation, and proliferation. CAR.IL-24-T cells inhibited CSC enrichment and exhibited stronger antitumor activity in vitro and in vivo.

Conclusions: IL-24 helps eliminate CSCs and endows CAR-T cells with improved antitumor reactivity.

MeSH terms

  • Cell Line, Tumor
  • Cell- and Tissue-Based Therapy
  • Humans
  • Immunotherapy, Adoptive
  • Interleukins*
  • Receptors, Chimeric Antigen*
  • Xenograft Model Antitumor Assays

Substances

  • Receptors, Chimeric Antigen
  • interleukin-24
  • Interleukins