HSV-tk gene therapy for human renal cell carcinoma in nude mice

We have treated Caki-2 human renal cell carcinoma in vivo using herpes simp lex virus thymidine kinase (HSV-tk) gene therapy. Both stably transduced Ca ki-2 tumors, generated using retrovirus-mediated ex vivo HSV-tk gene transf er and direct intratumoral adenovirus-mediated HSV-tk gene transfer of wild type tumors, were tested. Similar treatments with Lac Z containing retro- and adenoviruses were used as controls. The outcome was evaluated by imagin g the tumors before and after the treatment with magnetic resonance imaging , and using histology, immunocytochemistry, and survival analysis. When imp lanted orthotopically into nude mouse kidneys, Caki-2 cells formed reproduc ible cystic papillary kidney carcinomas. In vivo magnetic resonance imaging provided an important tool for the evaluation of tumor growth. Transductio n efficiency of wild-type tumors in vivo with adeno-Lac Z was 22 +/- 14%. S ignificant tumor regression was achieved with direct intratumoral adeno-HSV -tk transduction followed by intraperitoneal ganciclovir (GCV) (P<.001). Al so, the treatment of stably transduced Caki-2 tumors with intraperitoneal G CV resulted in a significant treatment response in the HSV-tk group as comp ared to the Lac<Zeta> group (P<.009). Increased apoptosis and macrophage in filtrations, reduced proliferation, and degenerative changes were observed in the tumors treated with HSV-tk and GCV. Also, significant prolongation i n survival was achieved with adeno-HSV-tk- and GCV-treated mice as compared to the controls. It is concluded that adeno-HSV-tk gene therapy may be use ful for the treatment of renal cell carcinoma in vivo.