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.

MATERIALS AND 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.

CONCLUSION

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.