Bioactive Materials (May 2023)
Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors
- 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
Affiliations
- Tao Chen
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China
- Yucheng Xue
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China
- Shengdong Wang
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China
- Jinwei Lu
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China
- Hao Zhou
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China
- Wenkan Zhang
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China
- Zhiyi Zhou
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, 310009, China
- Binghao Li
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China
- Yong Li
- Qingtian People's Hospital, Department of Orthopedics, Lishui, 323900, China
- Zenan Wang
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China
- Changwei Li
- 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
- Yinwang Eloy
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China
- Hangxiang Sun
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China
- Yihang Shen
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China
- Mohamed Diaty Diarra
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China
- Chang Ge
- Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China
- Xupeng Chai
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China
- Haochen Mou
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China
- Peng Lin
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China; Corresponding author. Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.
- Xiaohua Yu
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China; Corresponding author. Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.
- Zhaoming Ye
- Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China; Orthopaedic Research Institute, Zhejiang University, Hangzhou, 310009, China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China; Corresponding author. Orthopaedic Oncology Services, Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.
- Journal volume & issue
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Vol. 23
pp. 508 – 523
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.
