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Circulating nano-particulate TLR9 agonist scouts out tumor microenvironment to release immunogenic dead tumor cells.
- Source :
-
Oncotarget [Oncotarget] 2016 Aug 02; Vol. 7 (31), pp. 48860-48869. - Publication Year :
- 2016
-
Abstract
- Recent evidence suggest that a β-glucan derived from mushroom Schizophyllan(SPG) complexed with a humanized TLR9 agonistic CpG DNA, K3 (K3-SPG) is a promising vaccine adjuvant that induces robust CD8 T cell responses to co-administered antigen. However, it has not been investigated whether K3-SPG alone can act as an anti-cancer immunotherapeutic agent or not. Here, we demonstrate that intravenous injection of K3-SPG, but not CpG alone, is accumulated in the tumor microenvironment and triggered immunogenic cell death (ICD) of tumor cells by local induction of type-I interferon (IFN) as well as IL-12. Resultant innate immune activation as well as subsequent tumor-specific CD8 T cell responses were contributed the tumor growth suppression. This anti-tumor effect of K3-SPG monotherapy was also confirmed by using various tumor models including pancreatic cancer peritoneal dissemination model. Taken together, nano-particulate TLR9 agonist injected intravenously can scout out tumor microenvironment to provoke local innate immune activation and release dead tumor cells into circulation that may induce broader and protective tumor antigen-specific CD8 T cells.<br />Competing Interests: K.J.I., T.A., and K.K. filed a patent application related to the current work. T.A. is an employee for the Research Foundation of Microbial Diseases of Osaka University (BIKEN). M. H. is an employee for Mitsubishi Tanabe Pharma Corporation. N.K. is an employee for Zeria Pharmaceutical Co., ltd.
- Subjects :
- Adjuvants, Immunologic pharmacology
Animals
Antibody Formation
CD8-Positive T-Lymphocytes immunology
CpG Islands drug effects
Cytokines pharmacology
Humans
Immunity, Innate
Interferon Type I pharmacology
Interferon-gamma immunology
Interleukin-12 immunology
Leukocyte Common Antigens metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplasms blood
Oligodeoxyribonucleotides administration & dosage
Phagocytosis
Nanoparticles chemistry
Neoplasms immunology
Neoplasms therapy
Sizofiran pharmacology
Toll-Like Receptor 9 agonists
Tumor Microenvironment drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 31
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 27384490
- Full Text :
- https://doi.org/10.18632/oncotarget.10379