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PD‐1 Blockade Cellular Vesicles for Cancer Immunotherapy
Author(s) -
Zhang Xudong,
Wang Chao,
Wang Jinqiang,
Hu Quanyin,
Langworthy Benjamin,
Ye Yanqi,
Sun Wujin,
Lin Jing,
Wang Tianfu,
Fine Jason,
Cheng Hao,
Dotti Gianpietro,
Huang Peng,
Gu Zhen
Publication year - 2018
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.201707112
Subject(s) - immune system , cancer immunotherapy , tumor microenvironment , blockade , cancer research , immunotherapy , immune checkpoint , cd8 , cancer cell , cytotoxic t cell , melanoma , antibody , cancer , biology , materials science , receptor , microbiology and biotechnology , immunology , biochemistry , in vitro , genetics
Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD‐L1 that exhausts antigen‐specific CD8 + T cells through PD‐1 receptors. Checkpoint blockade antibodies against PD‐1 or PD‐L1 have shown unprecedented clinical responses. However, limited host response rate underlines the need to develop alternative engineering approaches. Here, engineered cellular nanovesicles (NVs) presenting PD‐1 receptors on their membranes, which enhance antitumor responses by disrupting the PD‐1/PD‐L1 immune inhibitory axis, are reported. PD‐1 NVs exhibit a long circulation and can bind to the PD‐L1 on melanoma cancer cells. Furthermore, 1‐methyl‐tryptophan, an inhibitor of indoleamine 2,3‐dioxygenase can be loaded into the PD‐1 NVs to synergistically disrupt another immune tolerance pathway in the tumor microenvironment. Additionally, PD‐1 NVs remarkably increase the density of CD8 + tumor infiltrating lymphocytes in the tumor margin, which directly drive tumor regression.