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

Menée in vitro et à l'aide d'un modèle murin, cette étude met en évidence un mécanisme par lequel l'interleukine IL-24, en ciblant les cellules souches cancéreuses, améliore l'efficacité des lymphocytes CAR-T

Résumé en anglais

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.