Cyclooxygenase-2 Inhibition Promotes Enhancement of Antitumor Responses by Transcutaneous Vaccination with Cytosine-Phosphate-Guanosine-Oligodeoxynucleotides and Model Tumor Antigen

One of the principal goals in tumor immune prophylaxis and tumor therapy is the induction of antitumor responses by generating sufficient numbers of tumor antigen-specific helper T (Th)1 cells and cytotoxic T lymphocytes (CTLs). We have demonstrated that the administration of cytosine-phosphate-guanosine-oligodeoxynucleotide (CpG-ODN) through tape-stripped skin induced a Th1-type immune response and suggested that the skin is a potential site for vaccination. CpG-ODN induces the expression of cyclooxygenase (COX)-2, and its product prostaglandin (PG) E2 underlies an immunosuppressive network, therefore it is a simple strategy to use a COX-2 inhibitor for tumor vaccination with CpG-ODN. In this study, we examined whether a COX-2 inhibitor enhances the antitumor immune response induced by CpG-ODN with model tumor antigen, ovalbumin (OVA), applied to tape-stripped skin in mice. The COX-2 inhibitor remarkably enhanced antigen-specific Th1-type immune responses and generation of CTLs induced by transcutaneous vaccination with CpG-ODN and OVA. PGE2 and IL-10 levels in the skin were significantly decreased and production of IL-12 was enhanced. This vaccination also induces an effective antitumor immunity in tumor-challenged mice. These results suggested that transcutaneous vaccination with a COX-2 inhibitor, CpG-ODN, and tumor antigen is a very simple and cost-effective strategy for tumor vaccine and may be readily achievable.