Suicide gene therapy of chemically induced mammary tumor in rat: efficacy and distant bystander effect.
We examined the efficacy of suicide gene therapy for nitrosomethylurea-induced mammary tumors in rats. Individual tumors were directly injected with a retrovirus-producing cell line that releases retroviral vectors that transduce the herpes simplex virus type 1 thymidine kinase (HSV1-TK) gene. HSV1-TK specifically converts the nucleoside analogue ganciclovir (GCV) into a toxic metabolite. Compared to control rats receiving saline, we observed a significant tumor regression of the injected tumors following GCV administration, accompanied by a stromal inflammation and an extensive lymphocyte infiltration invading the tumor epithelium. It is noteworthy that the neighboring uninjected tumors also regressed, demonstrating the occurrence of a distant bystander effect. This is the first demonstration that HSV1-TK/GCV can efficiently treat multiple solid tumors directly generated from an epithelial tissue.
Wei
M X
MX
Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Université Pierre et Marie Curie, Centre National de la Recherche Scientifique, Hôpital Pitié-Salpêtrière, Paris, France.
Bougnoux
P
P
Sacré-Salem
B
B
Peyrat
M B
MB
Lhuillery
C
C
Salzmann
J L
JL
Klatzmann
D
D
D000818:Animals; D000963:Antimetabolites / Q000378:metabolism / Q000627:therapeutic use*; D002273:Carcinogens; D005260:Female; D015774:Ganciclovir / Q000378:metabolism / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D008770:Methylnitrosourea; D009378:Neoplasms, Multiple Primary / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D014162:Transfection
D000963:Antimetabolites; D002273:Carcinogens; D008770:Methylnitrosourea; D013937:Thymidine Kinase; D015774:Ganciclovir