Abstract
The purpose of this study was to evaluate the efficacy of poly(lactic-co-glycolic acid) (PLGA)-based vaccines in breaking immunotolerance to cancer-associated self-antigens. Vaccination of mice bearing melanoma B16 tumors with PLGA nanoparticles (NP) co-encapsulating the poorly immunogenic melanoma antigen, tyrosinase-related protein 2 (TRP2), along with Toll-like receptor (TLR) ligand (7-acyl lipid A) was examined. Remarkably, this vaccine was able to induce therapeutic anti-tumor effect. Activated TRP2-specific CD8 T cells were capable of interferon (IFN)-gamma secretion at lymph nodes and spleens of the vaccinated mice. More importantly, TRP2/7-acyl lipid A-NP treated group has shown immunostimulatory milieu at the tumor microenvironment, as evidenced by increased level of pro-inflammatory cytokines compared to control group. These results support the potential use of PLGA nanoparticles as competent carriers for future cancer vaccine formulations.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Neoplasm / immunology*
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CD8-Positive T-Lymphocytes / immunology*
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Cancer Vaccines / immunology*
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Cells, Cultured
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Cytotoxicity, Immunologic / immunology
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Drug Carriers / therapeutic use
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Interferon-gamma / immunology
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Intramolecular Oxidoreductases / immunology
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Lactic Acid / administration & dosage
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Lactic Acid / therapeutic use*
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Lipid A / immunology
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Melanoma, Experimental / 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 / therapeutic use
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Polyglycolic Acid / administration & dosage
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Polyglycolic Acid / therapeutic use*
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Polylactic Acid-Polyglycolic Acid Copolymer
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Toll-Like Receptor 4 / immunology*
Substances
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Antigens, Neoplasm
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Cancer Vaccines
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Drug Carriers
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Lipid A
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TLR4 protein, human
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Toll-Like Receptor 4
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Polylactic Acid-Polyglycolic Acid Copolymer
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Polyglycolic Acid
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Lactic Acid
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Interferon-gamma
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Intramolecular Oxidoreductases
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dopachrome isomerase