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

K Pulkkanen, JJ Parkkinen, JM Laukkanen, MI Kettunen, K Tyynela, Risto Kauppinen, MY Ala-Opas, S Yla-Herttuala

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24 Citations (Scopus)

Abstract

We have treated Caki-2 human renal cell carcinoma in vivo using herpes simplex virus thymidine kinase (HSV-tk) gene therapy. Both stably transduced Caki-2 tumors, generated using retrovirus-mediated ex vivo HSV-tk gene transfer and direct intratumoral adenovirus-mediated HSV-tk gene transfer of wild type tumors, were tested. Similar treatments with LacZ containing retro- and adenoviruses were used as controls. The outcome was evaluated by imaging the tumors before and after the treatment with magnetic resonance imaging, and using histology, immunocytochemistry, and survival analysis. When implanted orthotopically into nude mouse kidneys, Caki-2 cells formed reproducible cystic papillary kidney carcinomas. In vivo magnetic resonance imaging provided an important tool for the evaluation of tumor growth. Transduction efficiency of wild-type tumors in vivo with adeno-LacZ was 22+/-14%. Significant tumor regression was achieved with direct intratumoral adeno-HSV-tk transduction followed by intraperitoneal ganciclovir (GCV) (P
Original languageEnglish
Pages (from-to)529-536
Number of pages8
JournalCancer Gene Therapy
Volume8
DOIs
Publication statusPublished - 1 Jul 2001

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