Electrofusion of syngeneic dendritic cells and tumor generates potent therapeutic vaccine |
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Authors: | Kjaergaard Jorgen Shimizu Keiji Shu Suyu |
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Affiliation: | Center for Surgery Research, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA. |
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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. |
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Keywords: | Dendritic cells Electrofusion DC-tumor hybrids Immunotherapy Vaccination |
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