Previous experiments have shown that a vascular endothelial growth factor (VEGF)-DT385 toxin conjugate inhibits endothelial cell proliferation, angiogenesis and solid tumor growth in a xenotransplant model system. Here, we report that VEGF-DT385 toxin conjugate effectively inhibits spontaneous tumorigenesis. The C3(1)/SV40 TAg transgenic mouse model of mammary gland carcinogenesis was used to determine the effectiveness of VEGF-DT385 toxin conjugate in delaying the onset of disease and the development of solid tumors. Animals were treated daily with conjugate for a period of 7 days. Therapy was initiated at week 14 of development before any visible adenocarcinomas were evident. Treatment of mice with VEGF-DT385 toxin conjugate significantly delayed the onset of tumorigenesis and inhibited solid tumor growth by more than 92%. Furthermore, conjugate treated animals showed less than twice the number of tumor nodules when compared to control mice. Finally, this vascular targeting agent significantly increased survival time of animals by 5 weeks. VEGF-DT385 toxin conjugate resulted in temporary weight loss and no long-lasting toxicity was seen. More importantly, using this established tumor model, VEGF-DT385 toxin conjugate appeared to be as effective as a similar treatment schedule with recombinant human endostatin. Our results suggest that VEGF-DT385 toxin conjugate is a potent inhibitor of mammary adenocarcinoma growth and might be useful in breast cancer therapy.
|Original language||English (US)|
|Number of pages||11|
|Journal||Breast Cancer Research and Treatment|
|State||Published - May 2004|
Bibliographical noteFunding Information:
This work was supported in part by, grants from NIH CA 71803, DAMD 17-99-1-9564 from USARMY, Sparboe and Women’s Health Fund Endowment (to S.R.) and a doctoral dissertation fellowship from the University of Minnesota Graduate School (to R.W.). We thank Dr Jeffrey E. Green (National Cancer Institute, NIH, Bethesda, MD) for providing the C3(1)/SV40 TAg transgenic mice. In addition, we thank Dr Roland Gunther (Division of Comparative Medicine, Department of Research Animal Resources, University of Minnesota, Minneapolis, MN) for histologic examination of tissues.
- Mammary carcinoma
- VEGF-DT385 toxin
- Vascular targeting