CpG oligonucleotides elicit antitumor responses in a human melanoma NOD/SCID xenotransplantation model.
For patients with advanced malignant melanoma, the 5 y survival rate with current treatment modalities is low. There is an urgent need for more effective therapeutic concepts. One approach with great potential is to stimulate the body's own immune defense to reject cancer cells using CpG oligonucleotides. Distinct oligonucleotides containing nonmethylated cytidine residues in cytidine-guanosine dinucleotides with particular flanking bases (CpG motifs) are capable of eliciting powerful immune stimulation by mimicking infectious disease. We evaluated the in vivo antitumoral effects of CpG oligonucleotides against human malignant melanoma xenografts in NOD/SCID mice. CpG oligonucleotides administered in single peritumoral subcutaneous injections three times per week resulted in elevated plasma levels of interleukin-12 and significant inhibition of the growth of established tumor xenografts by 60% (p<0.016) compared to the saline control. In addition to this a significant invasion of macrophages into tumor xenografts and increased numbers of Langerhans-cell-derived dendritic cells in draining lymph nodes could be observed. Our findings demonstrate the antitumor activity of oligonucleotides containing immune-stimulatory CpG motifs in a xenotransplantation model with absent B, T cells and a lack of natural killer cell function.
Department of Dermatology, Division of General Dermatology, University of Vienna, Austria.
Clemens
C
Krepler
Volker
V
Wacheck
Sabine
S
Strommer
Gunther
G
Hartmann
Peter
P
Polterauer
Klaus
K
Wolff
Hubert
H
Pehamberger
Burkhard
B
Jansen
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D018899:CpG Islands; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000097:blood; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009841:Oligonucleotides / Q000276:immunology / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D009841:Oligonucleotides; D018664:Interleukin-12