Suicide gene therapy with HSV-TK in pancreatic cancer has no effect in vivo in a mouse model

• Published in: European journal of surgical oncology 2003-11, Vol.29 (9), p.721-730
• Main Authors: Fogar, P., Greco, E., Basso, D., Habeler, W., Navaglia, F., Zambon, C.-F., Tormen, D., Gallo, N., Cecchetto, A., Plebani, M., Pedrazzoli, S.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; animal model; Animals; Antiviral Agents - therapeutic use; Applied cell therapy and gene therapy; Biological and medical sciences; Female; Ganciclovir - therapeutic use; Gastroenterology. Liver. Pancreas. Abdomen; Genetic Therapy; HSV-TK; Injections, Intraperitoneal; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Mice; Mice, SCID; pancreatic cancer; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Random Allocation; Retroviridae - genetics; Reverse Transcriptase Polymerase Chain Reaction; Simplexvirus - enzymology; Splenic Neoplasms - secondary; suicide gene therapy; Thymidine Kinase - genetics; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Tumor Cells, Cultured; Tumors; Xenograft Model Antitumor Assays
• ISSN: 0748-7983; 1532-2157
• DOI: 10.1016/j.ejso.2003.08.001

Aim: To study in vivo whether pancreatic cancer tumour growth and metastasis can be modified by a gene construct with HSV-TK suicide gene and IL2 co-expression. Methods: Seventy-eight female SCID mice were i.p. inoculated with retrovirally transduced or control MIA PaCa 2, CAPAN-1 and PANC-1 cell lines. The animals were then randomly selected for saline or ganciclovir (GCV) treatment from the second week, for a total of two weeks. Results: Most inoculated mice developed tumour nodules and spleen metastases. The liver was colonized by control CAPAN-1 and MIA PaCa 2, but not by PANC-1. Tumours in transduced MIA PaCa 2 cell injected mice were smaller, and in transduced CAPAN-1 injected mice larger, than in control-inoculated mice. There were increased pancreatic and decreased spleen metastases from transduced CAPAN-1, and diminished liver involvement from transduced MIA PaCa 2. No differences were found between mice inoculated with transduced and control PANC-1 cell lines. GCV treatment had no effect on tumour's size or metastases. Conclusions: The HSV-TK suicide gene does not confer GCV sensitivity to pancreatic cancer in this in vivo model. Different pancreatic cancer cell lines cause different growth and metastasis patterns after inoculation in SCID mice, possibly because of variations in their inherent characteristics. The different effects of our vector on cell growth and metastasis may be attributable to the effects of the immunostimulatory cytokine IL2.