• M Schmidt, A McWatters, R A White, B Groner, W Wels, Z Fan, and R C Bast.
• Division of Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4095, USA.
• Gynecol. Oncol. 2001 Feb 1; 80 (2): 145-55.

ObjectivesThe HER-2 proto-oncogene is overexpressed in 15-30% of ovarian cancers, providing a target for therapy in a fraction of patients. We previously described the ability of a recombinant single-chain anti-p185HER-2-Pseudomonas exotoxin A fusion protein, scFv(FRP5)-ETA, to inhibit growth of cancer cells in culture and tumor xenografts in vivo. We have also described synergistic interaction between an anti-p185HER-2-ricin A chain immunotoxin and ionizing radiation for inhibiting growth of ovarian and breast cancer cells that overexpress HER-2. Our objective in this report was to evaluate the in vitro and in vivo effects of scFv(FRP5)-ETA against SKOv3 ovarian cancer cells that have been transfected to express >10(6) p185HER-2 receptors per cell (clone-9002-18).MethodsInhibition of clonogenic growth was measured in vitro by limiting dilution analysis. Inhibition of tumor growth was measured in vivo using heterografts established with the same ovarian cancer cell lines.ResultsClone-9002-18 cells were substantially more sensitive than parental SKOv3 cells to the cytotoxic effects of scFv(FRP5)-ETA. Exotoxin fusion protein induced apoptosis in clone-9002-18 cells, but did not affect parental SKOv3 cells. Treatment of clone-9002-18 cells with 200- to 2000-cGy external beam irradiation in combination with scFv(FRP5)-ETA produced synergistic elimination of clonogenic tumor cells in culture. In vivo, subcutaneous or intraperitoneal growth of tumor xenografts in nu/nu mice was significantly inhibited (P = 0.004) by treatment for 10 days with scFv(FRP5)-ETA or with 131I-labeled-520C9 anti-p185HER-2 radionuclide conjugate, but additive effects were not observed with combined treatment.ConclusionScFv(FRP5)-ETA deserves further evaluation for intraperitoneal therapy of ovarian cancers that overexpress p185HER-2.

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