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Induction of anti-tumor immunity in mice using a syngeneic endothelial cell vaccine
1Department of Pathology, Stanford University Medical Center, Stanford, CA, USA.
Abstract:
Tumor endothelium could represent a novel target for active and passive immunotherapies of cancer. Here, we show that endothelial cells can be used as a vaccine in mice. In this study, three endothelial cell vaccine preparations from syngeneic (SVR), allogeneic (ISOS-1) and xenogeneic (ISO-HAS) sources were used to vaccinate mice. All mice developed humoral immune responses to endothelial cells and showed lower basal serum VEGF levels (37-45% lower) compared with unvaccinated control mice. Mice receiving the syngeneic SVR vaccine showed substantial inhibition of tumor growth after B16F10 melanoma challenge (50% of the mice in this group were tumor-free). The tumors that developed in the few mice in the syngeneic group had lower microvessel density counts (4-5 fold) compared with the other groups. The data suggests an in vivo antiangiogenic effect as the potential mechanism for the anti-cancer effect. In summary, further studies using other tumor models to demonstrate broad protection of this novel type of antiangiogenic vaccine are warranted.
Insights
Endothelial cells can be used as a novel cancer vaccine in mice, inducing immune responses and inhibiting tumor growth. This approach shows potential as an anti-cancer strategy by targeting tumor vasculature.
Area of Science:
- Oncology
- Immunology
- Vascular Biology
Background:
- The tumor endothelium presents a potential target for cancer immunotherapies.
- Developing novel strategies to target tumor vasculature is crucial for cancer treatment.
Purpose of the Study:
- To investigate the efficacy of endothelial cells as a vaccine in mice for cancer immunotherapy.
- To evaluate the anti-tumor effects and potential mechanisms of an endothelial cell-based vaccine.
Main Methods:
- Preparation and administration of syngeneic (SVR), allogeneic (ISOS-1), and xenogeneic (ISO-HAS) endothelial cell vaccines in mice.
- Assessment of humoral immune responses and serum VEGF levels post-vaccination.
- Evaluation of tumor growth inhibition and microvessel density in B16F10 melanoma-challenged mice.
Main Results:
- All vaccinated mice mounted humoral immune responses against endothelial cells.
- Vaccinated mice exhibited significantly lower basal serum VEGF levels (37-45% reduction).
- The syngeneic SVR vaccine demonstrated substantial inhibition of B16F10 melanoma growth, with 50% tumor-free mice and a 4-5 fold reduction in tumor microvessel density.
Conclusions:
- Endothelial cell vaccination can elicit anti-tumor immunity and reduce tumor vascularization.
- The observed anti-cancer effect is likely mediated by an in vivo antiangiogenic mechanism.
- Further research in diverse tumor models is warranted to confirm the broad applicability of this novel antiangiogenic vaccine.