Suicide gene therapy of ovarian cancer: an experimental study in rats using retroviral-mediated transfer of herpes simplex virus thymidine kinase gene.
BACKGROUND
This study evaluated the potential of gene therapy against ovarian cancer usin the retroviral transfer of the herpes simplex type 1 thymidine kinase gene (HSV1-TK) followed by ganciclovir treatment.


METHODS
The sensitivity of 4 different ovarian cancer cell lines (rat ar human) to in vitro infection by recombinant retroviruses were evaluated. Then, their HSV1-TK expressing derivatives were tested for their sensitivity to ganciclovir. One of them, DMBA-OC-1-TK+ was used to generate experimental ovarian cancer in 13 WKY female rats. After 14 days, tl rats received ganciclovir for 12 days (n = 6). The results were expressed in mean +/- ES and were evaluated with the Mann-Whitney test.


RESULTS
All cell lines analyzed in this study were sensitive to retroviral mediated gene transfer although with significant variations. The HSV 1-TK expressing derivatives of these cells were 300 7,000-fold more sensitive to ganciclovir, than the parental cells. The ganciclovir dramatically reduced the size of HSV1-TK+ tumors compared to untreated control rats (0 mm3 vs 2,594 mm3, p < 0.001) with complete tumor regression and residual fibrotic scars on pathological examination. Control tumors showed a poorly-differentiated epithelial adenocarcinoma of the ovary.


CONCLUSIONS
In a clinical perspective, the good tolerance and the significant anti-tumoral effects of retroviral-mediated transfer of HSV1-TK gene in animals were encouraging. It remains to set up gene transfer methods that will allow efficient targeting of the ovarian cancer in vivo.
Nagy
H J
HJ
Laboratoire de Recherche Chirurgicale, Hôpital Cochin, Université Paris, France.
Panis
Y
Y
Fabre
M
M
Klatzmann
D
D
Houssin
D
D
Soubrane
O
O
D016475:3T3 Cells; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D005814:Genes, Viral; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D023421:Models, Animal; D010051:Ovarian Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D013937:Thymidine Kinase / Q000008:administration & dosage / Q000235:genetics*
D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir