Immunogenicity and therapeutic efficacy of dendritic-tumor hybrid cells generated by electrofusion.
Dendritic cells (DCs) are potent antigen-presenting cells capable of inducing strong immune responses to weak tumor-associated antigens. Among various DC-based approaches, cancer immunotherapy with DC-tumor fusion hybrids offers advantages of polyclonal stimulation of a diverse array of tumor antigens. However, prevalent fusion methods using chemical fusogens such as polyethylene glycol often result in toxicity and low fusion efficiency. In this article, we describe an electrofusion technique, applicable to processing large numbers of cells with consistent and high fusion efficiency. Generation of fusion hybrids was verified by unequivocal experimental evidence. In animal models, fusion hybrids expressed the mature DC-like phenotype. They stimulated both CD4 and CD8 tumor-specific T cells to secrete interferon-gamma in vitro. In immunotherapy, a single vaccination with DC-tumor fusion cells along with interleukin-12 as an adjuvant eradicated tumors established in the skin nd lung. These results provide an impetus for treating cancer patients with similarly generated cells.
Center for Surgery Research, Cleveland Clinic Foundation, Ohio 44195, USA.
Takashi
T
Hayashi
Hiroshi
H
Tanaka
Junta
J
Tanaka
Rongfu
R
Wang
Bruce J
BJ
Averbook
Peter A
PA
Cohen
Suyu
S
Shu
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D006822:Hybrid Cells / Q000276:immunology*; D016167:Integrin alphaXbeta2 / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; D016167:Integrin alphaXbeta2; D008562:Membrane Glycoproteins; D018664:Interleukin-12; D007371:Interferon-gamma