HSV-1 thymidine kinase gene therapy for colorectal adenocarcinoma-derived peritoneal carcinomatosis.
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.
Lechanteur
C
C
Laboratory of Medical Oncology and Medical Chemistry, University of Liège, Belgium.
Princen
F
F
Lo Bue
S
S
Detroz
B
B
Fillet
G
G
Gielen
J
J
Bours
V
V
Merville
M P
MP
D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D000818:Animals; D000963:Antimetabolites / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D003131:Combined Modality Therapy; D015774:Ganciclovir / Q000627:therapeutic use; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D018259:Herpesvirus 1, Human / Q000201:enzymology; D009374:Neoplasms, Experimental; D010534:Peritoneal Neoplasms / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D051381:Rats; D015996:Survival Rate; D013937:Thymidine Kinase / Q000235:genetics*; D019076:Transgenes; D014407:Tumor Cells, Cultured
D000963:Antimetabolites; D013937:Thymidine Kinase; D015774:Ganciclovir