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Vaccine ; 26(39): 5046-57, 2008 Sep 15.
Article in English | MEDLINE | ID: mdl-18680779

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.


Subject(s)
Antigens, Neoplasm/immunology , CD8-Positive T-Lymphocytes/immunology , Cancer Vaccines/immunology , Lactic Acid/therapeutic use , Melanoma, Experimental/therapy , Polyglycolic Acid/therapeutic use , Toll-Like Receptor 4/immunology , Animals , Cells, Cultured , Cytotoxicity, Immunologic/immunology , Drug Carriers/therapeutic use , Interferon-gamma/immunology , Intramolecular Oxidoreductases/immunology , Lactic Acid/administration & dosage , Lipid A/immunology , Mice , Mice, Inbred C57BL , Nanoparticles/administration & dosage , Nanoparticles/therapeutic use , Polyglycolic Acid/administration & dosage , Polylactic Acid-Polyglycolic Acid Copolymer
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