Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors.

Abstract

Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy (ACT) against solid tumors. Here, we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors. Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+ T cells, which led to improved antitumor outcomes. Mechanistically, infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation. Overall, we presented a simple, cost-effective, and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.

• Authors: Tao Chen, Yucheng Xue, Shengdong Wang, Jinwei Lu, Hao Zhou, Wenkan Zhang, Zhiyi Zhou, Binghao Li, Yong Li, Zenan Wang, Changwei Li, Yinwang Eloy, Hangxiang Sun, Yihang Shen, Mohamed Diaty Diarra, Chang Ge, Xupeng Chai, Haochen Mou, Peng Lin, Xiaohua Yu, Zhaoming Ye
• Journal: Bioactive materials (Bioact Mater) Vol. 23 Pg. 508-523 (May 2023) ISSN: 2452-199X [Electronic] China
• PMID: 36514387 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors.