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 antige...

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Bibliographic Details
Published in:Clinical immunology (Orlando, Fla.) Fla.), 2002-07, Vol.104 (1), p.14-20
Main Authors: Hayashi, Takashi, Tanaka, Hiroshi, Tanaka, Junta, Wang, Rongfu, Averbook, Bruce J., Cohen, Peter A., Shu, Suyu
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - immunology
Antineoplastic agents
B7-1 Antigen - immunology
B7-2 Antigen
Biological and medical sciences
Cells, Cultured
dendritic cells
Dendritic Cells - cytology
Dendritic Cells - drug effects
Dendritic Cells - immunology
electrofusion
Humans
Hybrid Cells - immunology
Immunotherapy
Integrin alphaXbeta2 - immunology
Interferon-gamma - secretion
Interleukin-12 - immunology
Medical sciences
Membrane Glycoproteins - immunology
Mice
Mice, Inbred C57BL
Pharmacology. Drug treatments
T cells
Tumor Cells, Cultured
tumor immunity
vaccination
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Summary: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-γ 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.
ISSN:1521-6616
1521-7035
DOI:10.1006/clim.2002.5224