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Generation of functionally mature dendritic cells from elutriated monocytes using polyinosinic : polycytidylic acid and soluble CD40 ligand for clinical application

 S. Kim  ;  H. O. Kim  ;  H. J. Kim  ;  K. Lee  ;  H.-S. Kim 
 Clinical and Experimental Immunology, Vol.154(3) : 365-374, 2008 
Journal Title
 Clinical and Experimental Immunology 
Issue Date
CD40 Ligand/immunology* ; Cell Differentiation/immunology ; Cell Polarity/immunology ; Chemotaxis, Leukocyte/immunology ; Cytokines/biosynthesis ; Dendritic Cells/immunology* ; Humans ; Immunophenotyping ; Interferon Inducers/immunology ; Leukapheresis/methods ; Lymphocyte Culture Test, Mixed ; Monocytes/immunology ; Poly I-C/immunology* ; Th1 Cells/immunology ; Th2 Cells/immunology ; Tumor Necrosis Factor-alpha/immunology
dendritic cells ; elutriation ; functional activation ; maturation stimuli ; poly(I:C)
Despite the increasing use of dendritic cell (DC) vaccination in clinical trials, optimal conditions for the generation of functionally mature DCs remain to be established. The current standard DC maturation protocol for clinical trials has been used as an inflammatory cytokine cocktail [tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and prostaglandin E(2)], but this cocktail induced insufficient maturation of DCs derived from elutriated monocytes when cultured in X-VIVO 15. The aim of this study was to define effective combinations of stimulators for generating functionally mature DCs from elutriated monocytes under current good manufacturing practice conditions. We compared the functional capacity of DCs in response to all possible pairwise combinations of four different classes of stimuli: TNF-alpha, peptidoglycan, polyinosinic : polycytidylic acid [poly(I:C)] and soluble CD40 ligand (CD40L). Maturation status of DCs stimulated with combination of four stimuli was similar to that of the cytokine cocktail as assessed by the cell surface phenotype. However, only the combination of poly(I:C) + CD40L induced complete functional activation of the whole DC population, assessing IL-12p70 production, allostimulatory activity, migratory response to CCL19 and T helper 1-polarizing capacity. Thus, the protocol based on the combination of poly(I:C) and CD40L is more effective for the induction of clinical-grade DCs from elutriated monocytes than the standard cytokine cocktail.
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1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sin Young(김신영) ORCID logo https://orcid.org/0000-0002-2609-8945
Kim, Han Soo(김한수)
Kim, Hyun Ok(김현옥) ORCID logo https://orcid.org/0000-0002-4964-1963
Lee, Kyungwon(이경원) ORCID logo https://orcid.org/0000-0003-3788-2134
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