Armed with IL-2 based fusion protein improves CAR-T cell fitness and efficacy against solid tumors

Chimeric antigen receptor T (CAR-T) cell therapy is regarded as a potent immunotherapy and has made significant success in hematologic malignancies by eliciting antigen-specific immune responses. However, response rates of CAR-T cell therapy against solid tumors with immunosuppressive microenvironments remain limited. Co-engineering strategies are advancing methods to overcome immunosuppressive barriers and enhance antitumor responses. Here, we engineered an IL-2 mutein co-engineered CAR-T for the improvement of CAR-T cells against solid tumors and the efficient inhibition of solid tumors. We equipped the CAR-T cells with co-expressing both tumor antigen-targeted CAR and a mutated human interleukin-2 (IL-2m), conferring enhanced CAR-T cells fitness in vitro, reshaped immune-excluded TME, enhanced CAR-T infiltration in solid tumors, and improved tumor control without significant systemic toxicity. Overall, this subject demonstrates the universal CAR-T cells armed strategy for the development and optimization of CAR-T cells against solid tumors. •IL2m-CAR-T cells exhibit augmented proliferation in response to antigenic stimulation.•IL2m-CAR-T cells augment in vitro fitness including reduced exhaustion and improved memory characteristic of CAR-T cells.•IL2m-CAR-T cells promote TME remodeling including regulating PD-1 CD8+ T cells, NK, Treg and M2 macrophage.•IL2m-CAR-T cells have superior proliferation and antitumor activity in murine tumor models.