Therapeutic immune response induced by electrofusion of dendritic and tumor cells.
To elicit a therapeutic antitumor immune response, dendritic cells (DCs) have been employed as a cellular adjuvant. Among various DC-based approaches, fusion of DCs and tumor cells potentially confers not only DC functionality, but also a continuous source of unaltered tumor antigens. We have recently demonstrated successful generation of fusion hybrids by a large-scale electrofusion technique. The immunogenicity and therapeutic potential of fusion hybrids were further analyzed in a model system of a murine melanoma cell line expressing beta-galactosidase (beta-gal) as a surrogate tumor antigen. A single vaccination with fusion hybrids plus IL-12 induced a therapeutic immune response against 3-day established pulmonary metastases. This immunotherapy was beta-gal specific and involved both CD4 and CD8 T cells. In vitro, fusion hybrids stimulated specific IFN-gamma secretion from both CD4 and CD8 immune T cells. They also nonspecifically induced IL-10 secretion from CD4 but not CD8 T cells. Compared to other DC loadings, our results demonstrate the superior immunogenicity of fusion. The current technique of electrofusion is adequately developed for clinical use in cancer immunotherapy.
Tanaka
Hiroshi
H
Center for Surgery Research-FF50, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Shimizu
Keiji
K
Hayashi
Takashi
T
Shu
Suyu
S
D000276:Adjuvants, Immunologic; D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002459:Cell Fusion / Q000295:instrumentation / Q000379:methods*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004558:Electric Stimulation; D005260:Female; D006822:Hybrid Cells / Q000276:immunology* / Q000637:transplantation; D007155:Immunologic Factors / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D014611:Vaccination; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D007155:Immunologic Factors; D011993:Recombinant Fusion Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D001616:beta-Galactosidase