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

查看全文 作　　者：Tao [1,2,3]Chen;Yucheng [1,2,3]Xue;Shengdong [1,2,3]Wang;Jinwei [1,2,3]Lu;Hao [1,2,3]Zhou;Wenkan [1,2,3]Zhang;Zhiyi [4]Zhou;Binghao [1,2,3]Li;Yong [5]Li;Zenan [1,2,3]Wang;Changwei [6]Li;Yinwang [1,2,3]Eloy;Hangxiang [1,2,3]Sun;Yihang [1,2,3]Shen;Mohamed Diaty [1,2,3]Diarra;Chang [7]Ge;Xupeng [1,2,3]Chai;Haochen [1,2,3]Mou;Peng [1,2,3]Lin;Xiaohua [1,2,3]Yu;Zhaoming [1,2,3]Ye 高影响力作者 机构地区：[1]Orthopaedic Oncology Services,Department of Orthopaedics,The Second Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou,310009,China;[2]Orthopaedic Research Institute,Zhejiang University,Hangzhou,310009,China;[3]Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province,Hangzhou,310009,China;[4]The Second Clinical Medical College of Zhejiang Chinese Medical University,Hangzhou,310009,China;[5]Qingtian People’s Hospital,Department of Orthopedics,Lishui,323900,China;[6]Department of Orthopedics,Shanghai Key Laboratory for the Prevention and Treatment of Bone and Joint Diseases,Shanghai Institute of Traumatology and Orthopedics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,20025,China;[7]Department of Radiology,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,310009,China高影响力机构 出　　处：《Bioactive Materials》索引2023年第5期,共16页高影响力期刊 基　　金：This work was supported by National Natural Science Foundation of China(81872173,82072959,31870959,and 82102855);Zhejiang Province Natural Science Foundation(LY20H160018,LD21H160002,and LY19H160045). 摘　　要：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. 关 键 词：Adoptive cell therapy(ACT) Phage display Cell surface engineering Th9 cell Solid tumor
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