Enhancing the efficacy of a weak allogeneic melanoma vaccine by viral fusogenic membrane glycoprotein-mediated tumor cell-tumor cell fusion.
We have investigated how to make K1735 cells, a poor allogeneic melanoma vaccine, more effective for protection against B16 in vivo. To promote antigen release in an immunologically effective manner, tumor cells were transfected with a viral fusogenic membrane glycoprotein (vesicular stomatitis virus G glycoprotein), which kills cells through the formation, and degeneration, of large multinucleated syncytia. Vaccines consisting of a 1:1 mix of fusing allogeneic and autologous cells led to dramatic increases in survival of mice in both prophylactic and therapy models, dependent upon T cells, the mechanism of tumor-tumor cell fusion, and the nature of the fusion partner. Syncytia activate macrophages and fusogenic membrane glycoprotein-mediated cell killing very efficiently promotes cross-priming of immature dendritic cells with a model tumor antigen. Our data suggest that the unique manner in which syncytia develop and die provides a highly effective pathway for tumor antigen release and presentation to the immune system and offers a novel mechanism by which cancer cell vaccines may be prepared for clinical use.
D016475:3T3 Cells; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000276:immunology*; D016923:Cell Death / Q000276:immunology; D002459:Cell Fusion / Q000379:methods*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology; D004527:Egg Proteins / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments; D014759:Viral Envelope Proteins / Q000276:immunology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004527:Egg Proteins; C028391:G protein, vesicular stomatitis virus; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C110366:OVA-8; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; D010047:Ovalbumin