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

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. 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. 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. IL-24 helps eliminate CSCs and endows CAR-T cells with improved antitumor reactivity. © 2024. The Author(s), under exclusive licence to Springer Nature Limited.

Citation

Kai Zhang, Wenhao Hu, Feng Li, Chunli Wen, Lingxiao Zhou, Lei Zhang, Jingyao Lian, Shasha Liu, Shumin Wang, Yi Zhang. IL-24 improves efficacy of CAR-T cell therapy by targeting stemness of tumor cells. British journal of cancer. 2024 May;130(8):1337-1347

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PMID: 38347092

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