route of administration of the tlr9 agonist cpg critically determines the efficacy of cancer immunotherapy in micetlr9识别受体激动剂给药途径的cpg批判性决定癌症免疫治疗小鼠的疗效.pdfVIP

Route of Administration of the TLR9 Agonist CpG Critically Determines the Efficacy of Cancer Immunotherapy in Mice 1 1 1 1 1 Stefan Nierkens , Martijn H. den Brok , Thijs Roelofsen , Jori A. L. Wagenaars , Carl G. Figdor , Theo J. 2 1 Ruers , Gosse J. Adema * 1 Department of Tumor Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 2 The Netherlands Cancer Institute, Amsterdam, The Netherlands Abstract Background: The TLR9 agonist CpG is increasingly applied in preclinical and clinical studies as a therapeutic modality to enhance tumor immunity. The clinical application of CpG appears, however, less successful than would be predicted from animal studies. One reason might be the different administration routes applied in most mouse studies and clinical trials. We studied whether the efficacy of CpG as an adjuvant in cancer immunotherapy is dependent on the route of CpG administration, in particular when the tumor is destructed in situ. Methodology/Principal Findings: In situ tumor destruction techniques are minimally invasive therapeutic alternatives for the treatment of (nonresectable) solid tumors. In contrast to surgical resection, tumor destruction leads to the induction of weak but tumor-specific immunity that can be enhanced by coapplication of CpG. As in situ tumor destruction by cryosurgery creates an instant local release of antigens, we applied this model to study the efficacy of CpG to enhance antitumor immunity when administrated via different routes: peritumoral, intravenous, and subcutaneous but di