Nanocage-Therapeutics Prevailing Phagocytosis and Immunogenic Cell Death Awakens Immunity against Cancer

Authors
Lee, Eun JungNam, Gi-HoonLee, Na KyeongKih, MinwooKoh, EuneeKim, Yoon KyoungHong, YeonsunKim, SoyounPark, Seung-YoonJeong, CherlhyunYang, YoosooKim, In-San
Issue Date
2018-03-08
Publisher
WILEY-V C H VERLAG GMBH
Citation
ADVANCED MATERIALS, v.30, no.10
Abstract
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.
Keywords
SIRP-ALPHA; COMBINATION IMMUNOTHERAPY; HUMAN FERRITIN; DRUG-DELIVERY; TUMORS; NANOPARTICLE; THERAPY; CD47; NEOANTIGENS; MUTATIONS; SIRP-ALPHA; COMBINATION IMMUNOTHERAPY; HUMAN FERRITIN; DRUG-DELIVERY; TUMORS; NANOPARTICLE; THERAPY; CD47; NEOANTIGENS; MUTATIONS; CD47 blockade; immunogenic cell death; intrinsic anticancer vaccination; nanocages; therapeutics
ISSN
0935-9648
URI
https://pubs.kist.re.kr/handle/201004/121609
DOI
10.1002/adma.201705581
Appears in Collections:
KIST Article > 2018
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