期刊
CANCER RESEARCH
卷 64, 期 17, 页码 5934-5937出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-04-1261
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资金
- NCI NIH HHS [R01 CA057840-06, R01 CA080216-03, R01 CA095128-04, 1R01CA82016, 1R01CA57840, 1R01CA 095128] Funding Source: Medline
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-l-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 E-2 (PGE(2))-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 aDC1 allows, for the first time, the clinical application of DCs that combine the key three features important for their efficacy as anticancer vaccines.
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