alpha-type-1 polarized dendritic cells: a novel immunization tool with optimized CTL-inducing activity

Cancer Res. 2004 Sep 1;64(17):5934-7. doi: 10.1158/0008-5472.CAN-04-1261.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Polarity / immunology
  • Chemotaxis / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Interferon-alpha / immunology
  • Interferon-alpha / pharmacology
  • Interferon-gamma / immunology
  • Interferon-gamma / pharmacology
  • Interleukin-1 / immunology
  • Interleukin-1 / pharmacology
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / immunology
  • Ligands
  • Melanoma / blood
  • Melanoma / immunology
  • Poly I-C / immunology
  • Poly I-C / pharmacology
  • Protein Subunits / biosynthesis
  • Protein Subunits / immunology
  • Receptors, CCR7
  • Receptors, Chemokine / immunology
  • Receptors, Chemokine / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / pharmacology


  • CCR7 protein, human
  • Interferon-alpha
  • Interleukin-1
  • Ligands
  • Protein Subunits
  • Receptors, CCR7
  • Receptors, Chemokine
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Interferon-gamma
  • Poly I-C