1. ^*Department of Dermatology, Division of General Dermatology, University of Vienna, Austria
2. ^†Department of Clinical Pharmacology, Section of Experimental Oncology/Molecular Pharmacology, University of Vienna, Austria
3. ^‡Department of Clinical Pharmacology, University of Munich, Germany
4. ^§Department of Surgery, Section of Vascular Surgery, University of Vienna, Austria
5. ^¶Center of Excellence for Clinical and Experimental Oncology, University of Vienna, Austria
6. ^#Ludwig Boltzmann Institute for Clinical Experimental Oncology, Vienna, Austria
7. ^**Prostate Center, University of British Columbia, Vancouver, Canada

Correspondence: Volker Wacheck, MD, Department of Clinical Pharmacology, Section of Experimental Oncology/Molecular Pharmacology, Vienna General Hospital/University of Vienna, Waehringer Guertel 18–20; A-1090 Vienna, Austria. Email: Volker.Wacheck@univie.ac.at

Received 18 July 2002; Revised 21 July 2003; Accepted 14 August 2003; Published online 12 February 2004.

Abstract

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.