Electrofusion of a weakly immunogenic neuroblastoma with dendritic cells produces a tumor vaccine.
The absence of surface costimulatory molecules explains in part the lack of an effective anti-tumor immune response in tumor-bearing animals, even though unique tumor antigens may be presented by class I MHC. We determined that the immunogenicity of a murine neuroblastoma, Neuro-2a, which lacks surface costimulatory molecules, could be increased by electrically induced fusion with dendritic cells. Electrofusion induced a higher level of cell fusion than polyethylene glycol, and tumor/dendritic cell heterokaryons expressed high levels of costimulatory molecules. While Neuro-2a was unable to induce the proliferation of syngeneic or allogeneic T cells in vitro, fused cells were able to induce T cell responses both in vitro and in vivo. When fused dendritic tumor cells were used as a cancer vaccine, immunized mice were significantly protected from challenge with Neuro-2a. We propose that electrofusion with patient-derived tumor and dendritic cells may provide a rapid means to produce patient-specific tumor vaccines.
Orentas
R J
RJ
Department of Pediatrics, Section of Hematology-Oncology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA. rjo@mcw.edu
Schauer
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Bin
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Johnson
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D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D001854:Bone Marrow Cells / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002459:Cell Fusion; D003713:Dendritic Cells / Q000276:immunology*; D006183:H-2 Antigens / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006822:Hybrid Cells / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000401:mortality / Q000517:prevention & control; D009447:Neuroblastoma / Q000401:mortality / Q000517:prevention & control*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014407:Tumor Cells, Cultured; D014611:Vaccination / Q000379:methods
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019496:Cancer Vaccines; C497965:Cd86 protein, mouse; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D000949:Histocompatibility Antigens Class II; C111389:I-Ad antigen; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1