Synthetic double-stranded RNA poly(I:C) as a potent peptide vaccine adjuvant: therapeutic activity against human cervical cancer in a rodent model.
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.
Cui
Zhengrong
Z
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA. zhengrong.cui@oregonstate.edu
Qiu
Fu
F
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000187:drug effects; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000276:immunology; D027383:Papillomaviridae / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D012330:RNA, Double-Stranded / Q000276:immunology / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy*
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012330:RNA, Double-Stranded; C059731:oncogene protein E7, Human papillomavirus type 16