title: Electrofusion of syngeneic dendritic cells and tumor generates potent therapeutic vaccine.
abstract: Antigen presentation by dendritic cells (DCs) has the potential to elicit therapeutic immune responses against malignant tumors. One strategy utilizing DC-tumor fusion hybrids as cancer vaccine is particularly attractive because of polyclonal presentation of a diverse array of unaltered tumor antigens. We have recently developed a large-scale electrofusion technique for generating DC-tumor heterokaryons and demonstrated their superb immunogenicity. Here, employing the weakly immunogenic MCA205 sarcoma, a single vaccination with electrofusion hybrids eradicated tumors established in the lung, skin, and brain. Immunotherapy required intra-lymphoid vaccine delivery and co-administration of adjuvants such as OX-40R antibody. Tumor eradication was immunologically specific and involved the participation of both CD4 and CD8 T cells. Consistent with DC's functionality of MHC-restriction, the use of syngeneic DCs for fusion was an obligatory requirement. Fusion with allogeneic DCs completely lacked therapeutic effects. These findings provide a strong impetus for treating cancer patients with similarly generated DC-tumor hybrids.
authors.affiliation: Center for Surgery Research, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Jorgen
authors.initials: J
authors.lastname: Kjaergaard
authors.forename: Keiji
authors.initials: K
authors.lastname: Shimizu
authors.forename: Suyu
authors.initials: S
authors.lastname: Shu
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines; D002459:Cell Fusion; D017690:Cell Transplantation; D003713:Dendritic Cells / Q000276:immunology*; D016233:Immunotherapy, Active; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000276:immunology / Q000628:therapy*; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D014407:Tumor Cells, Cultured
chemical_list: D019496:Cancer Vaccines