Suicide gene therapy of chemically induced mammary tumor in rat: efficacy and distant bystander effect.

Abstract

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.

• Authors: M X Wei, P Bougnoux, B Sacré-Salem, M B Peyrat, C Lhuillery, J L Salzmann, D Klatzmann
• Journal: Cancer research (Cancer Res) Vol. 58 Issue 16 Pg. 3529-32 (Aug 15 1998) ISSN: 0008-5472 [Print] United States
• PMID: 9721854 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites
• Carcinogens
• Methylnitrosourea
• Thymidine Kinase
• Ganciclovir

Topics

• Animals
• Antimetabolites (metabolism, therapeutic use)
• Carcinogens
• Female
• Ganciclovir (metabolism, therapeutic use)
• Genetic Therapy (methods)
• Herpesvirus 1, Human (enzymology, genetics)
• Mammary Neoplasms, Experimental (chemically induced, pathology, therapy)
• Methylnitrosourea
• Neoplasms, Multiple Primary (chemically induced, pathology, therapy)
• Rats
• Rats, Sprague-Dawley
• Thymidine Kinase (genetics, metabolism, therapeutic use)
• Transfection