ENDOTHELIAL-CELL VEHICLES FOR DELIVERY OF CYTOTOXIC GENES AS A GENE-THERAPY APPROACH FOR CARCINOMA OF THE OVARY

Human umbilical vein endothelial cells (HUVECs) were evaluated for uti lity as a vector to achieve a bystander effect and killing of ovarian carcinoma cell lines, After demonstrating that HUVECs could be transdu ced with the reporter gene LacZ encoded by an adenoviral vector, appro priate cell killing of the AdCMVHSV-TK-transduced HUVECs was exhibited after treatment with 20 mu M ganciclovir, Mixing experiments were the n performed to determine whether the transduced HUVECs would demonstra te a bystander effect with the ovarian cancer cell lines, When 50% AdC MVHSV-TK-transduced HUVECs were mixed with untransduced ovarian cancer cells, >70% of all cells were killed, Finally, s,c, and i.p. injectio ns of herpes simplex-thymidine kinase-expressing HUVECs and SKOV3ip1 t umor cells were performed to evaluate the effects of HUVECs in in vivo models. These studies showed a decrease in tumor growth s,c, as well as a statistically significant survival prolongation (P < 0.05) in the i,p, model, These findings suggest that endothelial cells may be used as a vehicle for the delivery of cytotoxicity (bystander effect) in m olecular chemotherapy.