Abstract：
:Using the principle of functional polarization of dendritic cells (DCs), we have developed a novel protocol to generate human DCs combining the three features critical for the induction of type-1 immunity: (a) fully mature status; (b) responsiveness to secondary lymphoid organ chemokines; and (c) high interleukin-12p70 (IL-12p70)-producing ability. We show that IFN-alpha and polyinosinic:polycytidylic acid (p-I:C) synergize with the "classical" type-1-polarizing cytokine cocktail [tumor necrosis factor alpha (TNFalpha)/IL-1beta/IFNgamma], allowing for serum-free generation of fully mature type-1-polarized DCs (DC1). Such "alpha-type-1-polarized DC(s)" (alphaDC1) show high migratory responses to the CCR7 ligand, 6C-kine but produce much higher levels of IL-12p70 as compared to TNFalpha/IL-1beta/IL-6/prostaglandin E2 (PGE2)-matured DCs (sDC), the current "gold standard" in DC-based cancer vaccination. A single round of in vitro sensitization with alphaDC1 (versus sDCs) induces up to 40-fold higher numbers of long-lived CTLs against melanoma-associated antigens: MART-1, gp100, and tyrosinase. Serum-free generation of alphaDC1 allows, for the first time, the clinical application of DCs that combine the key three features important for their efficacy as anticancer vaccines.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Mailliard RB,Wankowicz-Kalinska A,Cai Q,Wesa A,Hilkens CM,Kapsenberg ML,Kirkwood JM,Storkus WJ,Kalinski Pdoi
10.1158/0008-5472.CAN-04-1261subject
Has Abstractpub_date
2004-09-01 00:00:00pages
5934-7issue
17eissn
0008-5472issn
1538-7445pii
64/17/5934journal_volume
64pub_type
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