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 ovar ian cancer usin the retroviral transfer. of the herpes simplex type 1 thymi dine kinase gene (HSV1-TK) followed by ganciclovir treatment. Materials and Methods: The sensitivity of 4 different ovarian cancer cell lines (rat ar human) to in vitro infection by recombinant retroviruses were evaluated. Th en, their HSV1-TK expressing derivatives were tested for their sensitivity to ganciclovir. One of them, DMBA-OC-1-TK+ was used to generate experimenta l ovarian cancer in 13 WKY female rats. After 14 days, tl rats received gan ciclovir for 12 days (n=6). The results were expressed in mean+/-ES and wer e evaluated with the Mann-Whitney test. Results: All cell lines analyzed in this study were sensitive to retroviral mediated gene transfe although wit h significant variations. The HSV1-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 ruts (0 mm(3) vs 2,594 mm(3), p<0.001) with complete tumor regression and residual fibrotic scars on pathological examination. C ontrol tumors showed a poorly-differentiated epithelial adenocarcinoma of t he ovary. Conclusion: In a clinical perspective, the good tolerance and the significant antitumoral effects of retroviral-mediated transfer of HSV1-TK gene in animals were encouraging. It remains to set up gene transfer metho ds that will allow efficient targeting of the ovarian cancer in vivo.