In the recent past, it has repeatedly been reported that CD4 cells play an important role in the immunology of chronic myeloid leukaemia. It was therefore of interest to test their activity in an animal model using bcr-abl-transformed cells. BALB/c mice were four times immunized with a DNA vaccine carrying the bcr-abl fusion gene. Two weeks after the last vaccine dose, the animals were challenged with syngeneic bcr-abl-transformed 12B1 cells which form solid tumors after subcutaneous administration. At the time of challenge, animals were treated with antibodies against the CD8+ T cells or CD4+ T cells. The efficacy of the depletion was monitored and found highly effective. All nonimmunized animals developed tumors. All animals untreated with the antibodies as well as those in which CD8+ T cells had been depleted, were fully protected against the challenge. On the other hand, almost all mice treated with anti-CD4+ antibody developed tumors. These results strongly suggested that the CD4+ T cells acted as effectors in the present system.

• MeSH
• fas Receptor immunology   metabolism   MeSH
• Fusion Proteins, bcr-abl genetics   immunology   MeSH
• CD4-Positive T-Lymphocytes immunology   metabolism   MeSH
• CD8-Positive T-Lymphocytes immunology   metabolism   MeSH
• Vaccines, DNA immunology   MeSH
• Immunization MeSH
• Humans MeSH
• Fas Ligand Protein metabolism   MeSH
• Lymphocyte Depletion MeSH
• Histocompatibility Antigens Class II immunology   metabolism   MeSH
• Disease Models, Animal MeSH
• Mice MeSH
• Cell Transformation, Neoplastic genetics   immunology   MeSH
• Neoplasms genetics   immunology   mortality   prevention & control   MeSH
• Cancer Vaccines genetics   immunology   MeSH
• Spleen cytology   immunology   MeSH
• Cell Line, Transformed 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
• fas Receptor MeSH
• Fusion Proteins, bcr-abl MeSH
• Vaccines, DNA MeSH
• Fas Ligand Protein MeSH
• Histocompatibility Antigens Class II MeSH
• Cancer Vaccines MeSH

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