Abstract
Dentritic cell (DC)-based cancer immunotherapy faces challenges in both efficacy and practicality. However, DC-based vaccination requires multiple injections and elaborates ex vivo manipulation, which substantially limits their use. Therefore, we sought to develop a chitosan nanoparticle (CH-NP)-based platform for the next generation of vaccines to bypass the ex vivo manipulation and induce immune responses via active delivery of polyinosinic-polycytidylic acid sodium salt (poly I:C) to target Toll-like receptor 3 (TLR3) in endosomes. We developed CH-NPs encapsulating ovalbumin (OVA) as a model antigen and poly I:C as the adjuvant in an ionic complex. These CH-NPs showed increased in vivo intracellular delivery to the DCs in comparison with controls after injection into tumor-bearing mice, and promoted DC maturation, leading to emergence of antigen-specific cytotoxic CD8+ T cells. Finally, the CH-NPs showed significantly greater antitumor efficacy in EG.7 and TC-1 tumor-bearing mice compared to the control (p < 0.01). Taken together, these data show that the CH-NP platform can be used as an immune response modulatory vaccine for active cancer immunotherapy without ex vivo manipulation, thus resulting in increased anticancer efficacy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / administration & dosage
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Animals
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Antigen Presentation / drug effects
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Antigens / administration & dosage
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Antigens / chemistry
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Antigens / immunology*
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Cancer Vaccines / administration & dosage
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Cancer Vaccines / chemical synthesis
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Chitosan / chemistry
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Chitosan / metabolism
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Dendritic Cells / cytology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Female
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Gene Expression
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Immunomodulation / drug effects
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Immunotherapy / methods*
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Lung Neoplasms / immunology
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Lung Neoplasms / pathology
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Lung Neoplasms / therapy*
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Lymphoma / immunology
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Lymphoma / pathology
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Lymphoma / therapy*
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Mice
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Mice, Inbred C57BL
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Nanoparticles / administration & dosage
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Nanoparticles / chemistry
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Nanotechnology / methods
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Ovalbumin / administration & dosage
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Ovalbumin / chemistry
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Ovalbumin / immunology*
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Poly I-C / administration & dosage*
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T-Lymphocytes, Cytotoxic / cytology
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T-Lymphocytes, Cytotoxic / drug effects
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T-Lymphocytes, Cytotoxic / immunology
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Toll-Like Receptor 3 / genetics
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Toll-Like Receptor 3 / immunology
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Transfection
Substances
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Adjuvants, Immunologic
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Antigens
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Cancer Vaccines
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TLR3 protein, mouse
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Toll-Like Receptor 3
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Ovalbumin
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Chitosan
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Poly I-C