Journal
ADVANCED MATERIALS
Volume 30, Issue 10, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201705581
Keywords
CD47 blockade; immunogenic cell death; intrinsic anticancer vaccination; nanocages; therapeutics
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Funding
- KU-KIST Graduate School of Converging Science and Technology Program
- KIST Institutional Program
- Ministry of Health and Welfare, Republic of Korea [1420390]
- National Research Foundation (NRF) of Korea - Korea government [NRF-2017R1A3B1023418]
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A growing appreciation of the relationship between the immune system and the tumorigenesis has led to the development of strategies aimed at re-editing the immune system to kill tumors. Here, a novel tactic is reported for overcoming the activation-energy threshold of the immunosuppressive tumor microenvironment and mediating the delivery and presentation of tumor neoantigens to the host's immune system. This nature-derived nanocage not only efficiently presents ligands that enhance cancer cell phagocytosis, but also delivers drugs that induce immunogenic cancer cell death. The designed nanocage-therapeutics induce the release of neoantigens and danger signals in dying tumor cells, and leads to enhancement of tumor cell phagocytosis and cross-priming of tumor specific T cells by neoantigen peptide-loaded antigen-presenting cells. Potent inhibition of tumor growth and complete eradication of tumors is observed through systemic tumor-specific T cell responses in tumor draining lymph nodes and the spleen and further, infiltration of CD8+ T cells into the tumor site. Remarkably, after removal of the primary tumor, all mice treated with this nanocage-therapeutics are protected against subsequent challenge with the same tumor cells, suggesting development of lasting, tumor-specific responses. This designed nanocage-therapeutics awakens the host's immune system and provokes a durable systemic immune response against cancer.
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