This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wei, M. X. Articles by Klatzmann, D. Search for Related Content PubMed PubMed Citation Articles by Wei, M. X. Articles by Klatzmann, D.

Suicide Gene Therapy of Chemically Induced Mammary Tumor in Rat: Efficacy and Distant Bystander Effect¹

Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Université Pierre et Marie Curie, Centre National de la Recherche Scientifique, Hôpital Pitié-Salpêtrière, 75651 Paris Cedex 13 [M. X. W., M-B. P., D. K.]; Génopoïétic, 75013 Paris [M. X. W.]; Laboratoire de Biologie des Tumeurs, Université François-Rabelais, 37044 Tours [P. B.]; Centre de Recherche, Département de Pathologie, Pfizer, 37401 Amboise [B. S-S.]; Laboratoire de Nutrition et Sécurité Alimentaire, Institut National de la Recherche Agronomique, Jouy en Josas [C. L.]; and Laboratoire d'Histologie, Université de Paris Nord., 93017 Bobigny [J-L. S.], France

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.

¹ This project was supported in part by the "Ligue Nationale Contre le Cancer" (Comité de Loir-et-Cher and Comité National) and ARDIVI (Association de la Recherche sur les Deficits Immunitaries Viro-Induit).

² To whom requests for reprints should be addressed, at CERVI, Hôpital Pitié-Salpêtrière, 83, Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.

Received 3/ 4/98. Accepted 7/ 1/98.

This article has been cited by other articles:

				Z. Qiu, J. S. Harms, J. Zhu, and G. A. Splitter Bovine Herpesvirus Tegument Protein VP22 Enhances Thymidine Kinase/Ganciclovir Suicide Gene Therapy for Neuroblastomas Compared to Herpes Simplex Virus VP22 J. Virol., April 15, 2004; 78(8): 4224 - 4233. [Abstract] [Full Text] [PDF]

				F. Denis, P. Bougnoux, L. Paon, O. le Floch, and F. Tranquart Radiosensitivity of Rat Mammary Tumors Correlates With Early Vessel Changes Assessed by Power Doppler Sonography J. Ultrasound Med., September 1, 2003; 22(9): 921 - 929. [Abstract] [Full Text] [PDF]

				V Pierrefite-Carle, P Baque, A Gavelli, N Brossette, D Benchimol, A Bourgeon, M C Saint Paul, P Staccini, and B Rossi Subcutaneous or intrahepatic injection of suicide gene modified tumour cells induces a systemic antitumour response in a metastatic model of colon carcinoma in rats Gut, March 1, 2002; 50(3): 387 - 391. [Abstract] [Full Text] [PDF]

				M. Mesnil and H. Yamasaki Bystander Effect in Herpes Simplex Virus-Thymidine Kinase/Ganciclovir Cancer Gene Therapy: Role of Gap-junctional Intercellular Communication1 Cancer Res., August 1, 2000; 60(15): 3989 - 3999. [Abstract] [Full Text]

				J. C. Morris Enzyme/Prodrug-Based Tumor Vaccination: All Politics (and Immunity) Are Local J Natl Cancer Inst, December 1, 1999; 91(23): 1986 - 1989. [Full Text] [PDF]

				V. Pierrefite-Carle, P. Baque, A. Gavelli, M. Mala, M. Chazal, J. Gugenheim, A. Bourgeon, G. Milano, P. Staccini, and B. Rossi Cytosine Deaminase/5-Fluorocytosine-Based Vaccination Against Liver Tumors: Evidence of Distant Bystander Effect J Natl Cancer Inst, December 1, 1999; 91(23): 2014 - 2019. [Abstract] [Full Text] [PDF]

				J. Galipeau, H. Li, A. Paquin, F. Sicilia, G. Karpati, and J. Nalbantoglu Vesicular Stomatitis Virus G Pseudotyped Retrovector Mediates Effective in Vivo Suicide Gene Delivery in Experimental Brain Cancer Cancer Res., May 1, 1999; 59(10): 2384 - 2394. [Abstract] [Full Text] [PDF]