Abstract
We have developed cell fusion vaccines generated with dendritic cells (DCs) and whole tumor cells to induce antigen-specific antitumor immunity. This approach allows DCs to be exposed to the entire repertoire of tumor-associated antigens (TAAs) originally expressed by the tumor cell, to process them endogenously, and to present antigenic epitopes thought the MHC class I and class II pathways to activate both CD8+ and CD4+ T cells, respectively. The therapeutic efficacy of DC/tumor fusion cell vaccines requires the improved immunogenicity of both cells. Here, we describe the strategy to generate DC/tumor fusion cells.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 9:271–296
Gong J, Chen D, Kashiwaba M et al (1997) Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nat Med 3:558–561
Koido S, Homma S, Okamoto M et al (2013) Fusions between dendritic cells and whole tumor cells as anticancer vaccines. Oncoimmunology 2:e24437
Koido S, Homma S, Hara E et al (2010) Regulation of tumor immunity by tumor/dendritic cell fusions. Clin Dev Immunol 2010:516768
Koido S, Hara E, Homma S et al (2007) Streptococcal preparation OK-432 promotes fusion efficiency and enhances induction of antigen-specific CTL by fusions of dendritic cells and colorectal cancer cells. J Immunol 178:613–622
Koido S, Hara E, Homma S et al (2007) Synergistic induction of antigen-specific CTL by fusions of TLR-stimulated dendritic cells and heat-stressed tumor cells. J Immunol 179:4874–4883
Koido S, Homma S, Okamoto M et al (2013) Combined TLR2/4-activated dendritic/tumor cell fusions induce augmented cytotoxic T lymphocytes. PLoS One 8:e59280
Koido S, Homma S, Okamoto M et al (2013) Augmentation of antitumor immunity by fusions of ethanol-treated tumor cells and dendritic cells stimulated via dual TLRs through TGF-beta1 blockade and IL-12p70 production. PLoS One 8:e63498
Akasaki Y, Kikuchi T, Irie M et al (2011) Cotransfection of Poly(I:C) and siRNA of IL-10 into fusions of dendritic and glioma cells enhances antitumor T helper type 1 induction in patients with glioma. J Immunother 34:121–128
Kikuchi T, Akasaki Y, Abe T et al (2004) Vaccination of glioma patients with fusions of dendritic and glioma cells and recombinant human interleukin 12. J Immunother 27:452–459
Gong J, Koido S, Chen D et al (2000) Immunization against murine multiple myeloma with fusions of dendritic and plasmacytoma cells is potentiated by interleukin 12. Blood 99:2512–2517
Iinuma H, Okinaga K, Fukushima R et al (2006) Superior protective and therapeutic effects of IL-12 and IL-18 gene-transduced dendritic neuroblastoma fusion cells on liver metastasis of murine neuroblastoma. J Immunol 176:3461–3469
Koide T, Iinuma H, Fukushima R (2009) Efficient CTL productivity of modified fusion cells by increase of heat shock protein 70. Oncol Rep 21:737–746
Rosenblatt J, Glotzbecker B, Mills H et al (2011) PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. J Immunother 34:409–418
Zhang M, Berndt BE, Chen JJ et al (2008) Expression of a soluble TGF-beta receptor by tumor cells enhances dendritic cell/tumor fusion vaccine efficacy. J Immunol 181:3690–3697
Weng D, Song B, Durfee J et al (2011) Induction of cytotoxic T lymphocytes against ovarian cancer-initiating cells. Int J Cancer 129:1990–2001
Zheng R, Cohen PA, Paustian CA et al (2008) Paired Toll-like receptor agonists enhance vaccine therapy through induction of interleukin-12. Cancer Res 68:4045–4049
Gong J, Zhang Y, Durfee J et al (2010) A heat shock protein 70-based vaccine with enhanced immunogenicity for clinical use. J Immunol 184:488–496
Terabe M, Ambrosino E, Takaku S et al (2009) Synergistic enhancement of CD8+ T cell-mediated tumor vaccine efficacy by an anti-transforming growth factor-beta monoclonal antibody. Clin Cancer Res 15:6560–6569
Ueda R, Fujita M, Zhu X et al (2009) Systemic inhibition of transforming growth factor-beta in glioma-bearing mice improves the therapeutic efficacy of glioma-associated antigen peptide vaccines. Clin Cancer Res 15:6551–6559
Conroy H, Galvin KC, Higgins SC et al (2012) Gene silencing of TGF-1 enhances antitumor immunity induced with a dendritic cell vaccine by reducing tumor-associated regulatory T cells. Cancer Immunol Immunother 61:425–431
Koido S, Homma S, Okamoto M et al (2013) Strategies to improve the immunogenicity of anticancer vaccines based on dendritic cell/malignant cell fusions. Oncoimmunology 2:e25994
Koido S, Gong J (2013) Characterization of structure and direct antigen presentation by dendritic/tumor-fused cells as cancer vaccines. Anticancer Res 33:347–354
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Koido, S., Gong, J. (2015). Cell Fusion Between Dendritic Cells and Whole Tumor Cells. In: Pfannkuche, K. (eds) Cell Fusion. Methods in Molecular Biology, vol 1313. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2703-6_13
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2703-6_13
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2702-9
Online ISBN: 978-1-4939-2703-6
eBook Packages: Springer Protocols