Induction of anti-tumor immunity in mice using a syngeneic endothelial cell vaccine.
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.
Scappaticci
F A
FA
Department of Pathology, Stanford University Medical Center, Stanford, CA, USA.
Nolan
G P
GP
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D002461:Cell Line, Transformed; D016228:Endothelial Growth Factors / Q000097:blood; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006390:Hemangioendothelioma / Q000473:pathology*; D006801:Humans; D007116:Immunization, Passive; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008222:Lymphokines / Q000097:blood; D008546:Melanoma, Experimental / Q000098:blood supply / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000517:prevention & control*; D010179:Pancreas / Q000166:cytology; D014407:Tumor Cells, Cultured / Q000637:transplantation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015415:Biomarkers; D019496:Cancer Vaccines; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors