Adoptive T cell therapy has achieved remarkable success in treating certain hematologic malignancies, but its efficacy against solid tumors remains limited due to various immunological challenges, including insufficient tumor infiltration, tumor cell immune tolerance, and an immunosuppressive tumor microenvironment (TME). This article reports a one-step cell engineering strategy that utilizes immune-boosting T cell fusion liposomes (referred to as IMPACTFUL) to enhance T cell efficacy against solid tumors.Through membrane fusion, IMPACTFUL is able to modify DPPA peptides on the surface of T cells while delivering magnetic nanoparticle cores loaded with interleukin-12 mRNA (MNP/IL-12) into the cytoplasm. The internalization of MNP/IL-12 enables T cells to achieve efficient tumor-targeting ability under the guidance of an external magnetic field and to reverse the immunosuppressive tumor microenvironment by expressing IL-12.The presentation of DPPA peptides enables T cells to overcome tumor cell immune tolerance by blocking the PD-L1 checkpoint. In mouse solid tumor models, T cells engineered with IMPACTFUL modifications were able to more effectively infiltrate tumors, resist exhaustion, and induce a tumor microenvironment more inclined toward inflammatory responses, thereby significantly inhibiting tumor growth compared to unmodified T cells.In summary, IMPACTFUL can endow T cells with multiple complementary functions through a single-step operation, thereby enhancing the efficacy of adoptive T cell therapy. This approach provides a versatile platform for improving the effectiveness of T cell therapy in treating solid tumors and is expected to accelerate its translation into clinical applications.

Original link

Advanced Materials ( IF 26.8 )

Pub Date : 2025-10-07

DOI: 10.1002/adma.202510842

Chunxiong Zheng,  Ke Yi,  Yongkang Du,  Qingguo Zhong,  Huimin Kong,  Haixia Wang,  Enguo Ju,  Yeh‐Hsing Lao,  Xi Xie,  Haochen Yao,  Yu Tao,  Mingqiang Li