Evaluation of herpes simplex thymidine kinase mediated gene therapy in experimental pancreatic cancer
2000; Wiley; Volume: 2; Issue: 5 Linguagem: Inglês
10.1002/1521-2254(200009/10)2
ISSN1521-2254
AutoresKimmo M�kinen, Sami Loimas, Jarmo Wahlfors, Esko Alhava, Juhani J�nne,
Tópico(s)CAR-T cell therapy research
ResumoThe Journal of Gene MedicineVolume 2, Issue 5 p. 361-367 Research Article Evaluation of herpes simplex thymidine kinase mediated gene therapy in experimental pancreatic cancer Kimmo Mäkinen, Corresponding Author Kimmo Mäkinen [email protected] Department of Surgery, Kuopio University Hospital, FIN-70211, Kuopio, Finland Gene Therapy Unit, Kuopio University Hospital, FIN-70211, Kuopio, Finland These two authors contributed equally to the work.Department of Surgery, Kuopio University Hospital, FIN-70211, Kuopio, Finland.Search for more papers by this authorSami Loimas, Sami Loimas Gene Therapy Unit, Kuopio University Hospital, FIN-70211, Kuopio, Finland A. I. Virtanen Institute, University of Kuopio, FIN-70211, Kuopio, Finland These two authors contributed equally to the work.Search for more papers by this authorJarmo Wahlfors, Jarmo Wahlfors Gene Therapy Unit, Kuopio University Hospital, FIN-70211, Kuopio, Finland A. I. Virtanen Institute, University of Kuopio, FIN-70211, Kuopio, FinlandSearch for more papers by this authorEsko Alhava, Esko Alhava Department of Surgery, Kuopio University Hospital, FIN-70211, Kuopio, Finland Gene Therapy Unit, Kuopio University Hospital, FIN-70211, Kuopio, FinlandSearch for more papers by this authorJuhani Jänne, Juhani Jänne Gene Therapy Unit, Kuopio University Hospital, FIN-70211, Kuopio, Finland A. I. Virtanen Institute, University of Kuopio, FIN-70211, Kuopio, FinlandSearch for more papers by this author Kimmo Mäkinen, Corresponding Author Kimmo Mäkinen [email protected] Department of Surgery, Kuopio University Hospital, FIN-70211, Kuopio, Finland Gene Therapy Unit, Kuopio University Hospital, FIN-70211, Kuopio, Finland These two authors contributed equally to the work.Department of Surgery, Kuopio University Hospital, FIN-70211, Kuopio, Finland.Search for more papers by this authorSami Loimas, Sami Loimas Gene Therapy Unit, Kuopio University Hospital, FIN-70211, Kuopio, Finland A. I. Virtanen Institute, University of Kuopio, FIN-70211, Kuopio, Finland These two authors contributed equally to the work.Search for more papers by this authorJarmo Wahlfors, Jarmo Wahlfors Gene Therapy Unit, Kuopio University Hospital, FIN-70211, Kuopio, Finland A. I. Virtanen Institute, University of Kuopio, FIN-70211, Kuopio, FinlandSearch for more papers by this authorEsko Alhava, Esko Alhava Department of Surgery, Kuopio University Hospital, FIN-70211, Kuopio, Finland Gene Therapy Unit, Kuopio University Hospital, FIN-70211, Kuopio, FinlandSearch for more papers by this authorJuhani Jänne, Juhani Jänne Gene Therapy Unit, Kuopio University Hospital, FIN-70211, Kuopio, Finland A. I. Virtanen Institute, University of Kuopio, FIN-70211, Kuopio, FinlandSearch for more papers by this author First published: 25 September 2000 https://doi.org/10.1002/1521-2254(200009/10)2:5 3.0.CO;2-7Citations: 26 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Background Despite of recent improvements in the treatment of many malignant diseases, pancreatic ductal adenocarcinoma is still a disease with an extremely poor prognosis with current modes of treatment. Gene therapy has been suggested as a novel approach also against pancreatic cancer. Previous studies have been carried out predominantly with immunodeficient animal models and with tumors growing in environments other than the pancreas. We have attempted to mimic a more clinically relevant situation and investigated suicide gene therapy strategy for experimental pancreatic cancer in animals with an intact immune system. Methods We used herpes simplex virus thymidine kinase (HSV-tk) and ganciclovir (GCV) strategy in both in vitro and in vivo settings. Results In vitro studies demonstrated that retro- as well as adenovirally transduced HSV-tk-positive DSL-6A/C1 rat pancreatic carcinoma cells were sensitive to low concentrations of GCV when compared with parental, nontransduced cells. In addition, a strong bystander effect was observed. In in vivo studies, subcutaneously transplanted HSV-tk-positive DSL-6A/C1 cells were killed after GCV treatment, whereas parental, HSV-tk-negative cells continued to grow and developed into ductal adenocarcinomas. In in vivo HSV-tk-transduced pancreatic tumors, GCV treatment caused tumor necrosis and the necrosis volume was significantly more extensive when compared with control groups. Conclusions HSV-tk gene transfer followed by GCV treatment is efficient in killing pancreatic cancer cells in vitro, in a transduced subcutaneous tumor model, as well as in in vivo transduced pancreatic tumors using an immunocompetent animal model. These results highlight the potential of gene therapy to treat experimental pancreatic cancer. Copyright © 2000 John Wiley & Sons, Ltd. References 1Gudjonsson B. Cancer of the pancreas: 50 years of surgery. Cancer 1987; 60: 2284– 2303. 2Alanen KA, Joensuu H. Long-term survival after pancreatic adenocarcinoma – often a misdiagnosis? Br J Cancer 1993; 68: 1004– 1005. 3Bramhall SR, Allum WH, Jones AG, Allwood A, Cummins C, Neoptolemos JP. 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