Human gene therapy vol:19 issue:10 pages:1101-1101
ESGCT Meeting location:Brugge, Belgium date:13-16 November 2008
Background: Effective induction of systemic cellular antitumor immunity is crucial for immunotherapeutic gene therapy against intracerebral gliomas. We examined in this study the in vivo efficacy of prophylactic subcutaneous (s.c.) immunization with dendritic cells (DC) transduced with lentiviral vectors (LV) in the GL261 orthotopic glioma model. Moreover, immune monitoring on brain infiltrating lymphocytes was performed.
Methods: VSV-G pseudotyped LV encoding eGFP driven by a CMV promoter (LV-eGFP) were produced in 293T cells under serum free conditions. Bone-marrow derived mouse DC were transduced ex vivo with these LV and matured with LPS. C57BL/6 mice were vaccinated with a s.c. injection of 1x106 DC and were subsequently stereotactically injected with GL261 glioma cells expressing eGFP. Control mice were left untreated. In both groups mice were sacrificed at day 5 (early) and day 30 (late) after tumor challenge: time points and tumor infiltrating lymphocytes were analysed by flowcytometry. Animals were clinically monitored for tumor-induced neurologic deficit and mortality was compared between the two groups.
Results and Conclusion: Although not protective, survival of DC treated mice was significantly prolonged compared to untreated animals (Logrank p<0.001). Both early and late immune monitoring revealed a significant increase in the absolute number of brain infiltrating lymphocytes. Moreover, total CD4+ and CD8+ as well as activated (CD44+) CD4+ and CD8+ T cells were significantly increased by DC treatment. These data underscore the feasibility of glioma immunotherapy based on ex vivo transduction of DC with lentiviral vectors.