Abstract
A novel method to improve targeting and presentation of poorly immunogenic tumor-related antigens was investigated. This was performed with a molecular adjuvant constructed by covalently linking a response selective peptide agonist of C5a (YSFKDMP(MeL)aR) to known melanoma tumor-related antigens. C57Bl/6J mice were injected subcutaneously with bone marrow derived dendritic cells (DCs) pulsed with a melanoma epitope (TRP2-P2/Agonist), melanoma epitope tyrosinase (TYR/Agonist), a nonfunctional reverse conformation C5a agonist bound to TYR(reverse peptide) or DMSO-PBS vehicle. Mice were injected with the pulsed DCs and cytokines IL-2 and GMCSF three times prior to subcutaneous challenge with B16-F10 melanoma cells. All groups subsequently received DC vaccine boosters twice per week. Tumor growth was reduced and survival enhanced in mice immunized with the combination of TRP2-P2/Agonist and TYR/Agonist compared to mice receiving reverse peptide or vehicle.
MeSH terms
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Animals
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology
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Antigens, Neoplasm / metabolism
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Cancer Vaccines / administration & dosage
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Cancer Vaccines / immunology*
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Cancer Vaccines / therapeutic use*
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Complement C5a / agonists*
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Complement C5a / genetics
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Complement C5a / therapeutic use
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Dendritic Cells / transplantation*
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Disease Models, Animal*
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Growth Inhibitors / administration & dosage
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Growth Inhibitors / metabolism
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Growth Inhibitors / therapeutic use
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Humans
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Interleukin-2 / metabolism
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Intramolecular Oxidoreductases / administration & dosage
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Intramolecular Oxidoreductases / metabolism
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Intramolecular Oxidoreductases / therapeutic use
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Melanoma, Experimental / genetics
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Melanoma, Experimental / immunology
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Melanoma, Experimental / prevention & control*
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Mice
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Mice, Inbred C57BL
Substances
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Antigens, Neoplasm
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Cancer Vaccines
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Growth Inhibitors
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Interleukin-2
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Complement C5a
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Intramolecular Oxidoreductases
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dopachrome isomerase