O. Schmidt1, 1Klinik und Poliklinik fuer Neurochirurgie, two Radiologische Klinik, and 3Klinik fuer Innere Medizin, Universitaetsklinikum HH Eppendorf, Hamburg, Germany Interleukin twelve has proven potent anti tumor activity through stimulation of the glioma suppressed cytotoxic T cell system. However, sys temic therapy is constrained by significant uncomfortable side effects. Neighborhood adenoviral mediated gene transfer has the probable to conquer this obstacle, but vector sys tems are needed that result in high and controllable transgene expression with minimized viral toxicity. The therapeutic efficiency of area IL 12 gene therapy was evaluated by intratumoral injection of adenoviral vectors while in the nicely established syngenic orthotopic glioma xenograft model. The adenoviral IL 12 transgene was under the manage of a bidirec tional promoter and a tetracycline suppressible transactivator that was cloned into the E1 area of an E1 deleted recombinant adenoviral vec tor.
One week following intratumoral injection of Ad. 3rmIL12, glioma development was inhibited by 73%, as assessed by T1 Gd enhanced MRI in contrast with selleck chemical tumors injected with NaCl or control adeno virus. Survival was Chondroitin drastically prolonged in Ad. 3rmIL12 taken care of animals, and a CD3 immunohistochemical examination demonstrated a sig nificantly higher intratumoral T cell infiltration. The treatment method appeared to get protected, as no side effects were observed. Transgene expression in vivo was localized in close vicinity towards the viral injection web site, as demonstrated by eGFP staining. The in vitro expression of IL twelve by GL261 glioma cells was significantly larger immediately after infection with Ad. 3rmIL twelve com pared with an adenoviral vector with transgene expression underneath the con trol of the standard CMV promoter. IL twelve expression immediately after infection with Ad.
3rmIL twelve was significantly suppressed during the pres ence of doxycycline. Regional in vivo gene treatment with Ad. 3rmIL 12 resulted within a increased reduction of tumor burden in contrast with Ad. CMV IL twelve in the identical dosage. Here, we demonstrated that neighborhood IL 12 gene therapy counterbalanced glioma induced immuno suppression by inducing

intratumoral T cell infiltration, which resulted in a significant reduction of tumor development. This new adenoviral vector system may contribute to the safety of viral gene therapy by resulting in more controllable and greater transgene expression than is obtained with standard CMV promoter driven vectors. ET 08. ROLE OF erbB2 Within the SENSITIVITY OF EGFR SIGNALING TO QUINAZOLINE BASED EGFR INHIBITORS IN GLIOMA CELL LINES Heather G. Gatcombe, Chi Ming Chang, and Hui Kuo G. Shu, Department of Radiation Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA Epidermal development factor receptor is overexpressed or ampli fied in roughly 50% of glioblastoma multiformes, and many of these tumors with amplified EGFR express a mutant, constitutively active form of this receptor, termed EGFRvIII.