Journal
ADVANCED MATERIALS
Volume 30, Issue 22, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201707112
Keywords
cancer immunotherapy; cell therapy; drug delivery; immune checkpoint blockade; nanomedicine
Categories
Funding
- Alfred P. Sloan Foundation
- NC TraCS, the National Institutes of Health (Clinical and Translational Science Award (CTSA, NIH)) [1L1TR001111]
- University of North Carolina (UNC) Cancer Center
- National Natural Science Foundation of China [31771036, 51703132, 51573096, 81401465]
- Basic Research Program of Shenzhen [JCYJ20170412111100742, JCYJ20160422091238319]
- Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China [161032]
- China Postdoctoral Science Foundation [2017M612742]
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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.
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