DNA vaccines showed great promise in preclinical models of infectious and malignant diseases, but their potency was insufficient in clinical trials and is needed to be improved. In this study, we tested systemic administration of two conventional adjuvants, synthetic oligodeoxynucleotide carrying immunostimulatory CpG motifs (CpG-ODN) and levamisole (LMS), and evaluated their effect on immune reactions induced by DNA vaccines delivered by a gene gun. DNA vaccination was directed either against the E7 oncoprotein of human papillomavirus type 16 or against the BCR-ABL1 oncoprotein characteristic for chronic myeloid leukemia. High doses of both adjuvants reduced activation of mouse splenic CD8(+) T lymphocytes, but the overall antitumor effect was enhanced in both tumor models. High-dose CpG-ODN exhibited a superior adjuvant effect in comparison with any combination of CpG-ODN with LMS. In summary, our results demonstrate the benefit of combined therapy with gene-gun-delivered antitumor DNA vaccines and systemic administration of CpG-ODN or LMS.

• MeSH
• Adjuvants, Immunologic administration & dosage   MeSH
• Fusion Proteins, bcr-abl genetics   immunology   metabolism   MeSH
• Biolistics MeSH
• CD8-Positive T-Lymphocytes drug effects   metabolism   pathology   MeSH
• Vaccines, DNA MeSH
• Neoplasms, Experimental immunology   pathology   therapy   MeSH
• Immunity drug effects   MeSH
• Levamisole administration & dosage   MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Mice, Inbred BALB C MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Oligodeoxyribonucleotides administration & dosage   MeSH
• Papillomavirus E7 Proteins genetics   immunology   metabolism   MeSH
• Cancer Vaccines * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adjuvants, Immunologic MeSH
• Fusion Proteins, bcr-abl MeSH
• CPG-oligonucleotide MeSH Browser
• Vaccines, DNA MeSH
• Levamisole MeSH
• Oligodeoxyribonucleotides MeSH
• Papillomavirus E7 Proteins MeSH
• Cancer Vaccines * MeSH

Infection with high-risk types of human papillomavirus (HPV) can cause the development of malignant tumors. To study mechanisms responsible for immune escape of tumor cells infected with HPV16, we previously used mouse oncogenic TC-1 cells producing HPV16 E6 and E7 oncoproteins to derive TC-1 clones resistant to immunization against E7. We have found immunoresistance of the clones to correlate with the point mutation in the E7 oncogene, which resulted in the N53S substitution in the immunodominant epitope RAHYNIVTF (aa 49-57). Here, we have shown that this mutation reduced stabilization of H-2D(b) molecules on RMA-S cells and eliminated immunogenicity of E7. The resistance of TC-1 clones was E7-specific as immunization against E6 inhibited tumor growth. Transduction of the TC-1/F9 clone carrying the mutated epitope with the wild-type E7 gene restored susceptibility to immunization against E7. Our results suggest that mutagenesis of tumor antigens can lead to the escape of malignant cells and should be considered in the development and evaluation of cancer immunotherapy.

• MeSH
• Antigens, Neoplasm chemistry   MeSH
• Point Mutation MeSH
• Epitopes chemistry   MeSH
• H-2 Antigens chemistry   MeSH
• Histocompatibility Antigen H-2D MeSH
• Immunodominant Epitopes chemistry   MeSH
• Immunotherapy methods   MeSH
• Humans MeSH
• Mutation MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Neoplasms immunology   metabolism   therapy   MeSH
• Oncogene Proteins, Viral chemistry   genetics   MeSH
• Oncogene Proteins chemistry   MeSH
• Papillomavirus E7 Proteins MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antigens, Neoplasm MeSH
• Epitopes MeSH
• H-2 Antigens MeSH
• Histocompatibility Antigen H-2D MeSH
• Immunodominant Epitopes MeSH
• oncogene protein E7, Human papillomavirus type 16 MeSH Browser
• Oncogene Proteins, Viral MeSH
• Oncogene Proteins MeSH
• Papillomavirus E7 Proteins MeSH