Evaluation of a xenogeneic VEGF vaccine in dogs with soft tissue sarcoma.

ABSTRACT

Active immunization against pro-angiogenic growth factors or their receptors is an emerging strategy for controlling tumor growth and angiogenesis. Previous studies in rodent tumor models have indicated that immunization against xenogeneic growth factors is more likely to induce effective anti-tumor responses than immunization against the autologous growth factor. However, the effectiveness or safety of the xenogeneic vaccination approach has not been previously assessed in a clinically relevant outbred, spontaneous tumor model. Therefore, we investigated the safety and anti-tumor and anti-angiogenic effects of a xenogeneic vascular endothelial cell growth factor (VEGF) vaccine in pet dogs with spontaneous cancer. Nine dogs with soft tissue sarcoma were immunized with a recombinant human VEGF vaccine over a 16-week period. The effects of immunization on antibodies to human and canine VEGF, circulating VEGF concentrations, tumor microvessel density (MVD), and tumor growth were assessed. The xenogeneic VEGF vaccine was well-tolerated by all dogs and resulted in induction of humoral responses against both human and canine VEGF in animals that remained in the study long enough to receive multiple immunizations. Three of five multiply immunized dogs also experienced sustained decreases in circulating plasma VEGF concentrations and two dogs had a significant decrease in tumor MVD. The overall tumor response rate was 30% for all treated dogs in the study. We conclude therefore that a xenogeneic VEGF vaccine may be a safe and effective alternative means of controlling tumor growth and angiogenesis.