The clinical grade maturation cocktail monophosphoryl lipid A plus IFNgamma generates monocyte-derived dendritic cells with the capacity to migrate and induce Th1 polarization.
Ex vivo generated monocyte-derived dendritic cells (DCs) are used as a cellular vaccine against cancer in clinical trials. In order to be able to induce an efficient tumour-specific CTL response during immunotherapy, DCs have to be able to migrate to the lymph node and produce the Th1 polarizing cytokine, IL-12p70, upon encounter of T cells in the lymph node. However, most clinically used DCs do not produce IL-12p70 upon T cell contact. In this study, we compared a newly developed clinical grade DC maturation cocktail consisting of MPLA and IFNgamma with two clinically available maturation cocktails, the 'gold standard' (TNFalpha, IL-1beta, IL-6 and PGE(2)) and the 'alpha type 1 polarizing' (TNFalpha, IL-1beta, IFNalpha, IFNgamma and pI:C) cocktail. All three cocktails induced phenotypically mature DCs. However, in contrast to 'gold standard' DCs, which produce no IL-12p70 and as a result induce mainly Th2 cells, DCs matured with MPLA and IFNgamma produce high levels of IL-12p70 upon CD40 triggering. Subsequently, these DCs induce mainly Th1 cells in vitro, even slightly more than by the alpha type 1 polarized DCs. In addition, MPLA plus IFNgamma matured DCs have an intermediate migratory capacity towards CCL21. In conclusion, we here present MPLA plus IFNgamma as a simple clinical grade maturation cocktail to generate immunostimulatory DCs with superior capacity to induce type 1 immunity.
Ten Brinke
Anja
A
Department of Immunopathology, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Center, Amsterdam, The Netherlands. a.tenbrinke@sanquin.nl
Karsten
Miriam L
ML
Dieker
Miranda C
MC
Zwaginga
Jaap Jan
JJ
van Ham
S Marieke
SM
D049109:Cell Proliferation; D002633:Chemotaxis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D018664:Interleukin-12 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology
D008050:Lipid A; D018664:Interleukin-12; D007371:Interferon-gamma; C048436:monophosphoryl lipid A