Activating CD8+ T Cells by Pt(IV) Prodrug-Based Nanomedicine and aPD-L1 Antibody for Enhanced Cancer Immunotherapy

被引:9
|
作者
Wang, Bin [1 ,2 ]
Zhou, Jingyu [2 ,3 ,4 ]
Li, Ruitong [5 ]
Tang, Dongsheng [1 ,2 ]
Cao, Zheng [6 ]
Xu, Chun [7 ]
Xiao, Haihua [1 ,2 ]
机构
[1] Chinese Acad Sci, Beijing Natl Lab Mol Sci, Lab Polymer Phys & Chem, Inst Chem, Beijing 100190, Peoples R China
[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[3] Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Mol Med, Hangzhou 310024, Zhejiang, Peoples R China
[4] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
[5] Nankai Univ, Coll Chem, Dept Chem, Tianjin 300071, Peoples R China
[6] Univ Calif Los Angeles, Dept Chem & Biomol Engn, Los Angeles, CA 90095 USA
[7] Univ Queensland, Sch Dent, Brisbane, Qld 4006, Australia
基金
中国国家自然科学基金;
关键词
chemotherapy; immunotherapy; immunogenic cell death; tumor immune microenvironment; TRANS-RETINOIC ACID; THERAPY;
D O I
10.1002/adma.202311640
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Recent years have witnessed substantial progress in cancer immunotherapy, specifically T cell-based therapies. However, the application of T cell therapies has been primarily limited to hematologic malignancies, with limited success in the treatment of solid tumors. The main challenge in treating solid tumor is immune escape, which is characterized by reduced antigenicity, diminished immunogenicity, and the development of suppressive tumor immune microenvironments. To address these obstacles and restore T cell-mediated anti-tumor responses, a novel nanoparticle formulation known as PRA@Oxa-c16 is developed. This innovative approach combines retinoic acid and Pt(IV) to specifically target and overcome immune escape. Notably, the therapeutic efficacy of PRA@Oxa-c16 primarily relies on its ability to induce anti-tumor T cell responses, in contrast to the cytotoxicity associated with conventional chemotherapeutic agents. When combined with an immune checkpoint blockade, anti-programmed death-ligand 1 antibody, PRA@Oxa-c16 effectively eliminates solid tumors and induces immune memory responses, which prevent tumor metastasis and recurrence. This promising approach holds great potential for enhancing the treatment of solid tumors with T cell-based immunotherapy.
引用
收藏
页数:15
相关论文
共 22 条
  • [1] Open-Source Throttling of CD8+ T Cells in Brain with Low-Intensity Focused Ultrasound-Guided Sequential Delivery of CXCL10, IL-2, and aPD-L1 for Glioblastoma Immunotherapy
    Dong, Lei
    Zhu, Yini
    Zhang, Haoge
    Gao, Lin
    Zhang, Zhiqi
    Xu, Xiaoxuan
    Ying, Leqian
    Zhang, Lu
    Li, Yue
    Yun, Zhengcheng
    Zhu, Danqi
    Han, Chang
    Xu, Tingting
    Yang, Hui
    Ju, Shenghong
    Chen, Xiaoyuan
    Zhang, Haijun
    Xie, Jinbing
    ADVANCED MATERIALS, 2024, 36 (44)
  • [2] 4-1BB-Enhanced Expansion of CD8+ TIL from Triple-Negative Breast Cancer Unveils Mutation-Specific CD8+ T Cells
    Harao, Michiko
    Forget, Marie-Andree
    Roszik, Jason
    Gao, Hui
    Babiera, Gildy V.
    Krishnamurthy, Savitri
    Chacon, Jessica A.
    Li, Shumin
    Mittendorf, Elizabeth A.
    DeSnyder, Sarah M.
    Rockwood, Korrene F.
    Bernatchez, Chantale
    Ueno, Naoto T.
    Radvanyi, Laszlo G.
    Vence, Luis
    Haymaker, Cara
    Reuben, James M.
    CANCER IMMUNOLOGY RESEARCH, 2017, 5 (06) : 439 - 445
  • [3] Roseburia intestinalis generated butyrate boosts anti-PD-1 efficacy in colorectal cancer by activating cytotoxic CD8+ T cells
    Kang, Xing
    Liu, Changan
    Ding, Yanqiang
    Ni, Yunbi
    Ji, Fenfen
    Lau, Harry Cheuk Hay
    Jiang, Lanping
    Sung, Joseph J. Y.
    Wong, Sunny H.
    Yu, Jun
    GUT, 2023, 72 (11) : 2112 - 2122
  • [4] Prostate cancer cells synergistically defend against CD8+ T cells by secreting exosomal PD-L1
    Li, Dameng
    Zhou, Xueying
    Xu, Wenxian
    Chen, Yuxin
    Mu, Chenglong
    Zhao, Xinchun
    Yang, Tao
    Wang, Gang
    Wei, Liang
    Ma, Bo
    CANCER MEDICINE, 2023, 12 (15): : 16405 - 16415
  • [5] Low CD8+ T Cell Infiltration and High PD-L1 Expression Are Associated with Level of CD44+/CD133+ Cancer Stem Cells and Predict an Unfavorable Prognosis in Pancreatic Cancer
    Hou, Ya-Chin
    Chao, Ying-Jui
    Hsieh, Min-Hua
    Tung, Hui-Ling
    Wang, Hao-Chen
    Shan, Yan-Shen
    CANCERS, 2019, 11 (04)
  • [6] Irradiation Suppresses IFNγ-Mediated PD-L1 and MCL1 Expression in EGFR-Positive Lung Cancer to Augment CD8+ T Cells Cytotoxicity
    Wang, Chun-I.
    Chang, Yi-Fang
    Sie, Zong-Lin
    Ho, Ai-Sheng
    Chang, Jung-Shan
    Peng, Cheng-Liang
    Cheng, Chun-Chia
    CELLS, 2021, 10 (10)
  • [7] Anti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific CD8+ T Cell Response in Hepatocellular Carcinoma
    Pena-Asensio, Julia
    Calvo, Henar
    Torralba, Miguel
    Miquel, Joaquin
    Sanz-de-Villalobos, Eduardo
    Larrubia, Juan-Ramon
    CANCERS, 2021, 13 (08)
  • [8] In Vivo Expansion of Activated Naive CD8+ T Cells and NK Cells Driven by Complexes of IL-2 and Anti-IL-2 Monoclonal Antibody As Novel Approach of Cancer Immunotherapy
    Tomala, Jakub
    Chmelova, Helena
    Mrkvan, Tomas
    Rihova, Blanka
    Kovar, Marek
    JOURNAL OF IMMUNOLOGY, 2009, 183 (08) : 4904 - 4912
  • [9] Blocking exposed PD-L1 elicited by nanosecond pulsed electric field reverses dysfunction of CD8+ T cells in liver cancer
    Qian, Junjie
    Chen, Tianchi
    Wu, Qinchuan
    Zhou, Lin
    Zhou, Wuhua
    Wu, Liming
    Wang, Shuai
    Lu, Jiahua
    Wang, Wenchao
    Li, Dazhi
    Xie, Haiyang
    Su, Rong
    Guo, Danjing
    Liu, Zhen
    He, Ning
    Yin, Shengyong
    Zheng, Shusen
    CANCER LETTERS, 2020, 495 : 1 - 11
  • [10] CD137L dendritic cells induce potent response against cancer-associated viruses and polarize human CD8+ T cells to Tc1 phenotype
    Dharmadhikari, Bhushan
    Nickles, Emily
    Harfuddin, Zulkarnain
    Ishak, Nur Diana Binte
    Zeng, Qun
    Bertoletti, Antonio
    Schwarz, Herbert
    CANCER IMMUNOLOGY IMMUNOTHERAPY, 2018, 67 (06) : 893 - 905