Tumor associated antigen and interleukin-12 mRNA transfected dendritic cells enhance effector function of natural killer cells and antigen specific T-cells.
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.
Bontkes
Hetty J
HJ
VU University Medical Center, Department of Pathology, Amsterdam, The Netherlands. hj.bontkes@vumc.nl
Kramer
Duco
D
Ruizendaal
Janneke J
JJ
Meijer
Chris J L M
CJ
Hooijberg
Erik
E
D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D000951:Antigens, Neoplasm; D016207:Cytokines; D020382:Interleukin-18; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D018664:Interleukin-12