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α-type-1 polarized dendritic cells: A novel immunization tool with optimized CTL-inducing activity

Lookup NU author(s): Professor Catharien Hilkens


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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-α and polyinosinic:polycytidylic acid (p-I:C) synergize with the "classical" type-1-polarizing cytokine cocktail [tumor necrosis factor α (TNFα)/IL-1β/IFNγ], allowing for serum-free generation of fully mature type-1-polarized DCs (DC1). Such "α-type-1-polarized DC(s)" (αDC1) show high migratory responses to the CCR7 ligand, 6C-kine but produce much higher levels of IL-12p70 as compared to TNFα/IL-1β/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 αDC1 (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 αDC1 allows, for the first time, the clinical application of DCs that combine the key three features important for their efficacy as anticancer vaccines.

Publication metadata

Author(s): Mailliard RB, Wankowicz-Kalinska A, Cai Q, Wesa A, Hilkens CM, Kapsenberg ML, Kirkwood JM, Storkus WJ, Kalinski P

Publication type: Article

Publication status: Published

Journal: Cancer Research

Year: 2004

Volume: 64

Issue: 17

Pages: 5934-5937

Print publication date: 01/09/2004

ISSN (print): 0008-5472

ISSN (electronic): 1538-7445

Publisher: American Association for Cancer Research


DOI: 10.1158/0008-5472.CAN-04-1261

PubMed id: 15342370


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Funder referenceFunder name
1R01CA 095128NCI NIH HHS
R01 CA095128-04NCI NIH HHS
R01 CA057840-06NCI NIH HHS
R01 CA080216-03NCI NIH HHS