Synthetic double-stranded RNA poly(I:C) as a potent peptide vaccine adjuvant: therapeutic activity against human cervical cancer in a rodent model.

Abstract

Due to the inherent lack of immunogenicity of peptides, it is generally recognized that the strong inflammatory signals that are required to elicit specific responses against peptide-based therapeutic tumor vaccines may not be provided by the standard/conventional vaccine adjuvants. In this study, we have demonstrated dsRNA in the form of synthetic pI:C as a potent adjuvant to enhance the specific anti-tumor immune responses against a peptide-based vaccine. When complexed with an MHC I-restricted minimal peptide epitope derived from the HPV 16 E7 protein, the resulting pI:C/E7(49-57) molecular complex induced strong E7(49-57)-specific CTL responses that caused significant regressions of model human cervical cancer tumors pre-established in mice. In addition, although the proportion of DCs in tumor-bearing mice was significantly decreased when compared to that in naïve mice, immunization with pI:C/E7(49-57 )restored the proportion of DCs in tumor-bearing mice. Double-stranded RNA may hold a great potential as an adjuvant to induce cellular immune responses for tumor immunotherapy.