Paracrine Release of IL-12 Stimulates IFN-γ Production and Dramatically Enhances the Antigen-Specific T Cell Response after Vaccination with a Novel Peptide-Based Cancer Vaccine

• DOI: 10.4049/jimmunol.172.9.5159
• Publication Date: 2014-04-21T00:08:23Z
• Authors: Mohamed L. Salem; Andre N. Kadima; Yuehua Zhou; Christophe L. Nguyen; Mark P. Rubinstein; Marina Demcheva; John N. Vournakis; David J. Cole; William E. Gillan...
• Keywords: Ovalbumin; Egg Proteins; Melanoma, Experimental; Antigen-Presenting Cells; Epitopes, T-Lymphocyte; Mice, Transgenic; CD8-Positive T-Lymphocytes; Adoptive Transfer; Cancer Vaccines; Interleukin-12; Peptide Fragments; 3. Good health; Mice, Inbred C57BL; Interferon-gamma; Mice; 03 medical and health sciences; 0302 clinical medicine; Adjuvants, Immunologic; Cell Line, Tumor; Paracrine Communication; Animals; Gels; Immunologic Memory

Abstract Interleukin-12 can act as a potent adjuvant for T cell vaccines, but its clinical use is limited by toxicity. Paracrine administration of IL-12 could significantly enhance the response to such vaccines without toxicity associated with systemic administration. We have developed novel vaccine delivery system (designated F2 gel matrix) composed poly-N-acetyl glucosamine that has dual properties sustained-release and adjuvant. To test efficacy paracrine IL-12, we incorporated this cytokine into matrix monitored OT-1 cells in an adoptive transfer model. Recipient mice were vaccinated gel/SIINFEKL, gel/SIINFEKL/IL-12 (paracrine IL-12), or gel/SIINFEKL plus (systemic IL-12). Systemic levels lower IL-12-treated mice, suggesting may be less However, was enhanced Ag-specific proliferative functional response. Furthermore, promoted generation stable, memory population protection from tumor challenge. study mechanisms underlying response, wild-type gene-deficient used. The immune reduced IFN-γ−/− IL-12Rβ2−/− recipient role mediated, at least part, host cells. Collectively, results support potential suggest sustained release application.