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Tumor associated antigen and interleukin-12 mRNA transfected dendritic cells enhance effector function of natural killer cells and antigen specific T-cells

Authors
Journal
Clinical Immunology
1521-6616
Publisher
Elsevier
Publication Date
Volume
127
Issue
3
Identifiers
DOI: 10.1016/j.clim.2008.02.001
Keywords
  • Human
  • Dendritic Cells
  • Natural Killer Cells
  • Cytokines
  • Vaccination
Disciplines
  • Medicine

Abstract

Abstract Immunotherapy aiming at the combined activation of tumor associated antigen (TAA) specific cytotoxic T lymphocytes (CTL) and Natural Killer (NK) cells may be crucial to eradicate both MHC-I positive and negative tumors. Vaccination with mature dendritic cells (DC) transfected with mRNA encoding for TAA and the pro-inflammatory cytokines interleukin (IL)-12 and IL-18 may increase NK cell and TAA specific CTL activity. We demonstrate here that IL-12 over-expressing human DC induces increased NK cell activation and effector function and confirm the increase in TAA specific CTL by TAA/IL-12 double transfected DC. The effects of IL-18 transfection were limited to phenotypic activation and down-regulation of tissue homing receptors and did not add to the effect of IL-12 on NK cell effector function. In conclusion, co-transfection of TAA and IL-12 mRNA into mature DCs offers a vaccine for the induction of an anti-tumor immune response mediated by CTL and NK effector cells.

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