Nejvíce citovaný článek - PubMed ID 19724931
DNA vaccination against bcr-abl-positive cells in mice
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
- antigeny CD95 imunologie metabolismus MeSH
- bcr-abl fúzní proteiny genetika imunologie MeSH
- CD4-pozitivní T-lymfocyty imunologie metabolismus MeSH
- CD8-pozitivní T-lymfocyty imunologie metabolismus MeSH
- DNA vakcíny imunologie MeSH
- imunizace MeSH
- lidé MeSH
- ligand Fas metabolismus MeSH
- lymfocytární deplece MeSH
- MHC antigeny II. třídy imunologie metabolismus MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nádorová transformace buněk genetika imunologie MeSH
- nádory genetika imunologie mortalita prevence a kontrola MeSH
- protinádorové vakcíny genetika imunologie MeSH
- slezina cytologie imunologie MeSH
- transformované buněčné linie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny CD95 MeSH
- bcr-abl fúzní proteiny MeSH
- DNA vakcíny MeSH
- ligand Fas MeSH
- MHC antigeny II. třídy MeSH
- protinádorové vakcíny 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
- adjuvancia imunologická aplikace a dávkování MeSH
- bcr-abl fúzní proteiny genetika imunologie metabolismus MeSH
- biolistika MeSH
- CD8-pozitivní T-lymfocyty účinky léků metabolismus patologie MeSH
- DNA vakcíny MeSH
- experimentální nádory imunologie patologie terapie MeSH
- imunita účinky léků MeSH
- levamisol aplikace a dávkování MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- oligodeoxyribonukleotidy aplikace a dávkování MeSH
- Papillomavirus E7 - proteiny genetika imunologie metabolismus MeSH
- protinádorové vakcíny * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adjuvancia imunologická MeSH
- bcr-abl fúzní proteiny MeSH
- CPG-oligonucleotide MeSH Prohlížeč
- DNA vakcíny MeSH
- levamisol MeSH
- oligodeoxyribonukleotidy MeSH
- Papillomavirus E7 - proteiny MeSH
- protinádorové vakcíny * MeSH