Systemic administration of CpG oligodeoxynucleotide and levamisole as adjuvants for gene-gun-delivered antitumor DNA vaccines.
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.
Department of Experimental Virology, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague 2, Czech Republic. smahel@uhkt.cz
Michal
M
Šmahel
Ingrid
I
Poláková
Eva
E
Sobotková
Eva
E
Vajdová
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D019470:Biolistics; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007109:Immunity / Q000187:drug effects; D007978:Levamisole / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D009838:Oligodeoxyribonucleotides; D050725:Papillomavirus E7 Proteins; D019444:Vaccines, DNA; D007978:Levamisole; D016044:Fusion Proteins, bcr-abl