A clinical grade cocktail of cytokines and PGE2 results in uniform maturation of human monocyte-derived dendritic cells: implications for immunotherapy.
Dendritic cells (DCs) can induce tumor- or pathogen-specific T cell responses in humans. We comprehensively compared the clinically available DC maturation stimuli for their ability to promote uniformly mature DCs that elicit higher levels of T cell responses. We compared the standard maturation stimulus, autologous monocyte-conditioned medium (MCM), with a synthetic double stranded RNA (poly I:C), soluble CD40 ligand trimer, and a defined cocktail of cytokines (TNF-alpha, IL-1 beta, IL-6) and PGE(2) to promote mature phenotype and function in human monocyte-derived DCs. The cocktail was the most efficient despite the lack of induction of IL-12p70. While these results support the use of the MCM-mimic cocktail in clinical DC immunotherapy trials, the roles of it's individual constituents remain to be completely defined.
Lee
Andrew W
AW
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021, USA.
Truong
Tuan
T
Bickham
Kara
K
Fonteneau
Jean-Francois
JF
Larsson
Marie
M
Da Silva
Ida
I
Somersan
Selin
S
Thomas
Elaine K
EK
Bhardwaj
Nina
N
D002455:Cell Division / Q000276:immunology; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000166:cytology*
D017077:Culture Media, Conditioned; D016207:Cytokines; D018664:Interleukin-12; D007371:Interferon-gamma; D015232:Dinoprostone