Similar efficiency of DNA-liposome complexes and retrovirus-producing cells for HSV-tk suicide gene therapy of peritoneal carcinomatosis.
Several experimental approaches have been tested for suicide gene delivery into tumor cells, including viral and non-viral vectors. In this study, we compared the efficiency of Herpes Simplex Virus type 1 thymidine kinase gene (HSV-tk) delivery by retrovirus-producing cells and DNA/liposome complexes for the treatment of peritoneal carcinomatosis induced in syngeneic rats by DHD/K12 colorectal adenocarcinoma cells. After in vitro determination of the best transduction conditions, rats were treated with multiple intraperitoneal injections of plasmid DNA containing one or two copies of CMV-driven HSV-tk gene (pCMV-TK and p(CMV-TK)2, respectively) associated with LipofectAMINE, each injection being followed by a Ganciclovir (GCV) course. Animals treated by DNA/liposome complexes and GCV or with retrovirus-producing cells and GCV showed a similar increase of survival as compared to the control group. After DNA/ liposome injections, expression of the tk transgene was detected in tumor nodes (epiploon) and also in liver, lung, spleen, bowels and brain. The expression was not homogeneous throughout the different organs and most likely reflected the transfection of only a limited number of cells.
Princen
F
F
Laboratory of Medical Chemistry and Medical Oncology, University of Liège, Belgium.
Lechanteur
C
C
Lopez
M
M
Gielen
J
J
Bours
V
V
Merville
M P
MP
D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D017931:DNA Primers; D004279:DNA, Viral / Q000008:administration & dosage; D004195:Disease Models, Animal; D015774:Ganciclovir / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000235:genetics; D008081:Liposomes; D010534:Peritoneal Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D010957:Plasmids; D016133:Polymerase Chain Reaction; D051381:Rats; D011919:Rats, Inbred Strains; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013937:Thymidine Kinase / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D017931:DNA Primers; D004279:DNA, Viral; D008081:Liposomes; D013937:Thymidine Kinase; D015774:Ganciclovir