Analyses for the enhancing methods of tumor vaccination therapy in cancer-bearing hosts

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We previously have shown that nona-arginine (R9)-PTD induced efficient protein-antigen (Ag) transduction of dendritic cells (DCs) in vitro, resulting in the efficient induction of strong Ag-specific immune responses mediated by CD8+ and CD4+ T cells and in superior antitumor effects in vivo. In the present study, we investigated the immune responses caused by intradermal (i.d.) injections of R9-PTD-containing protein Ags without DC preparation. We found that i.d. injections of recombinant R9-ovalbumin fusion protein (rR9-OVA) into naive C57BL/6 mice elicited OVA-specific CTLs and produced IgG2-dominant immunoglobulin. The i.d. injections of rR9-OVA also induced inflammatory cell infiltrations containing neutrophils, monocytes, and lymphocytes, as well as inflammatory cytokine productions, such as IFN-gamma, IL-2, IP-10, with presenting SIINFEKL-epitopes on MHC class I molecules at the injection area. Intratumoral injections of rR9-OVA into EG.7-tumor mass significantly suppressed tumor growth, and these effects were completely abrogated by the depletion of CD8+ T cells. These results indicate that i.d. injections of rR9-containing immunogenic Ag simultaneously induce dual immunological effects: the induction of Tc1- and Th1-dominant immune responses, and the induction of inflammatory and CTL-mediated immune responses at the injection area by expressing Ag-epitopes onto MHC class I molecules as targets.