Physical interaction between dendritic cells and tumor cells results in an immunogen that induces protective and therapeutic tumor rejection.
Dendritic cells (DCs) are potent professional APCs capable of presenting Ag in the context of costimulatory signals necessary for T cell activation. Although tumor cells express target Ags, they are generally incapable of stimulating an immune response. We show that the short term physical interaction of DCs and tumor cells, with or without cell fusion, results in rapid, efficient, and stable DC-tumor cell association. Immunization of naive mice with unselected, irradiated DC-tumor cell conjugates induces tumor-specific CD8+ cytotoxic T cells and protection from lethal tumor challenge. Furthermore, the immunogenicity of this cellular vaccine is dependent on the physical interaction of DCs and tumor cells before injection. Immunization with DCs and tumor cells after physical interaction can result in the regression of established tumors and persistent antitumor immunity. These results suggest that immunization with DC-tumor cell vaccines may be a simple, rapid, and potent strategy for tumor immunotherapy.
Celluzzi
C M
CM
Department of Dermatology, University of Pittsburgh School of Medicine, PA 15213, USA.
Falo
L D
LD
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002459:Cell Fusion / Q000276:immunology; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008175:Lung Neoplasms / Q000276:immunology* / Q000628:therapy; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines