2001 Abstract: 1798 Antiangiogenic Gene Therapy Delays Growth of Murine and Human Pancreatic Adenocarcinoma in Mice
Abstracts 2001 Digestive Disease Week
# 1798 Antiangiogenic Gene Therapy Delays Growth of Murine and Human Pancreatic Adenocarcinoma in Mice Jennifer F. Tseng, Filip A. Farnebo, Oliver Kisker, Christian M. Becker, Calvin J. Kuo, Judah Folkman, Richard C. Mulligan, Boston, MA
Introduction: Pancreatic adenocarcinoma has a poor prognosis; conventional therapies offer minimal benefit. Since angiogenesis is required for solid tumor growth, antiangiogenic gene therapy may be a means to combat this malignancy. We investigated the effects of an adenovirus encoding an angiogenesis factor receptor on pancreatic adenocarcinoma growth in mice.
Methods: A recombinant adenovirus was constructed encoding Flk-1, a receptor for vascular endothelial growth factor (VEGF). Sixteen immunocompetent C57Bl/6 mice were injected subcutaneously with 5¥105 syngeneic murine pancreatic adenocarcinoma Panc02 cells. Sixteen immunodeficient SCID C57Bl/6 mice were injected with 106 BxPc-3 human pancreatic adenocarcinoma cells. In both groups, when tumors had reached 100-150 mm3 in volume, half the mice were injected with 109 Flk-1 adenovirus particles and half with control virus. Plasma Flk-1 levels were measured by ELISA. Tumor volumes were measured twice weekly.
Results: Flk-1 was detected at concentrations of 2-8 mg/ml by day 3 in treated mice. 3 weeks after injection of adenovirus, tumor curves diverged between the Flk-1 and control arms in both the murine (figure) and human pancreatic groups. After 6 weeks, Ad-Flk-1 treatment had resulted in 75% smaller murine and 85% smaller human pancreatic adenocarcinomas (p<0.001).
Conclusion: A recombinant adenovirus encoding the VEGF receptor Flk-1 slowed tumor growth in mice bearing both human and murine pancreatic adenocarcinomas. Antiangiogenic gene therapy may be useful in the future treatment of patients with pancreatic cancer.