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.
Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Université Pierre et Marie Curie, Centre National de la Recherche Scientifique, Hôpital Pitié-Salpêtrière, Paris, France.
M X
MX
Wei
P
P
Bougnoux
B
B
Sacré-Salem
M B
MB
Peyrat
C
C
Lhuillery
J L
JL
Salzmann
D
D
Klatzmann
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