Electrofusion of syngeneic dendritic cells and tumor generates potent therapeutic vaccine.
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.
Kjaergaard
Jorgen
J
Center for Surgery Research, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Shimizu
Keiji
K
Shu
Suyu
S
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
D019496:Cancer Vaccines