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Published on: July 17, 2013
Evaluation of a xenogeneic VEGF vaccine in dogs with soft tissue sarcoma
Debra Kamstock1, Robyn Elmslie, Douglas Thamm
1Department of Microbiology, Colorado State University, Ft Collins, CO 80523, USA.
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.
Insights
A xenogeneic vascular endothelial cell growth factor (VEGF) vaccine showed promise in controlling canine cancer. This novel approach was well-tolerated and induced anti-tumor responses, suggesting potential for future cancer therapies.
Area of Science:
- Oncology
- Immunology
- Veterinary Medicine
Background:
- Active immunization against pro-angiogenic factors is an emerging cancer therapy strategy.
- Xenogeneic growth factor immunization shows greater efficacy than autologous in rodent models.
- Clinical relevance of xenogeneic vaccination in spontaneous tumor models is unassessed.
Purpose of the Study:
- To evaluate the safety and efficacy of a xenogeneic vascular endothelial cell growth factor (VEGF) vaccine.
- To assess anti-tumor and anti-angiogenic effects in a canine cancer model.
- To investigate immune responses to xenogeneic VEGF vaccination.
Main Methods:
- Nine pet dogs with spontaneous soft tissue sarcoma were immunized with a recombinant human VEGF vaccine over 16 weeks.
- Assessed antibody induction to human and canine VEGF, circulating VEGF levels, tumor microvessel density (MVD), and tumor growth.
- Monitored vaccine tolerance and adverse events throughout the study.
Main Results:
- The xenogeneic VEGF vaccine was well-tolerated in all dogs.
- Humoral responses against human and canine VEGF were induced in multiply immunized dogs.
- Sustained decreases in circulating VEGF and tumor MVD were observed in some dogs, with a 30% overall tumor response rate.
Conclusions:
- Xenogeneic VEGF vaccination is a safe and potentially effective strategy for controlling tumor growth and angiogenesis.
- This approach demonstrates promise in a clinically relevant outbred, spontaneous tumor model.
- Further research into xenogeneic VEGF vaccines for cancer treatment is warranted.
