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Novel C5a Agonist-Based Dendritic Cell Vaccine in a Murine Model of Melanoma

Volume 6, Issue 22   November 15, 2007
Pages 2835 - 2839
http://dx.doi.org/10.4161/cc.6.22.4899
Authors: Anthony A. Floreani, Sandra J. Gunselman, Arthur J. Heires, Ralph J. Hauke, Stefano Tarantolo and John D. Jackson

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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 GM-CSF 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.

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