HSV-1 thymidine kinase gene therapy for colorectal adenocarcinoma-derived peritoneal carcinomatosis

Gene Therapy
C LechanteurM P Merville

Abstract

Peritoneal carcinomatosis is a common clinical situation which, in most cases, cannot be eradicated by surgery or chemotherapy. The feasibility of an HSV-TK-based suicide gene therapy for peritoneal carcinomatosis induced by DHD/K12 colon carcinoma cells was investigated. DHD/K12 cells stably expressing the tk gene were killed in vitro in the presence of low concentrations of ganciclovir, they exhibited a 'bystander effect' when mixed with TK-negative cells. BD-IX rats injected intraperitoneally, either directly or after surgical peritoneal irritations, with DHD/K12 cells developed peritoneal carcinomatosis within 2 weeks. Ganciclovir treatment of animals injected with DHD/K12-TK cells allowed a significant reduction of the tumor volume as well as a prolonged survival. Of these animals 35-40% showed a long-term disease-free survival after ganciclovir therapy. Residual or relapsing tumors could be explained by a low expression of the transgene as demonstrated by RT-PCR.

Citations

Aug 19, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Seung-Hee HongIn-Hoo Kim
May 18, 2006·American Journal of Physiology. Endocrinology and Metabolism·Kyoichiro TsuchiyaYukio Hirata
Apr 30, 2003·World Journal of Gastroenterology : WJG·Xiang-Ming XuBing-Liang Fang

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