aerosolized bc-819 inhibits primary but not secondary lung cancer growth雾化bc - 819抑制肺癌主要但不是次要的增长.pdfVIP

Aerosolized BC-819 Inhibits Primary but Not Secondary Lung Cancer Growth ¨ 1 1 1 2 1 Gunther Hasenpusch , Corinna Pfeifer , Manish Kumar Aneja , Kai Wagner , Dietrich Reinhardt , Michal 3 3 3 1 ¤ Gilon , Patricia Ohana , Avraham Hochberg , Carsten Rudolph * 1 Department of Pediatrics, Ludwig-Maximilians-University, Munich, Germany, 2 Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany, 3 Department of Biological Chemistry, Institute of Life Sciences, Hebrew University, Jerusalem, Israel Abstract Despite numerous efforts, drug based treatments for patients suffering from lung cancer remains poor. As a promising alternative, we investigated the therapeutic potential of BC-819 for the treatment of lung cancer in mouse tumor models. BC-819 is a novel plasmid DNA which encodes for the A-fragment of Diphtheria toxin and has previously been shown to successfully inhibit tumor growth in human clinical study of bladder carcinoma. In a first set of experiments, we examined in vitro efficacy of BC-819 in human lung cancer cell-lines NCI-H460, NCI-H358 and A549, which revealed .90% reduction of cell growth. In vivo efficacy was examined in an orthotopic mouse xenograft lung cancer model and in a lung metastasis model using luminescent A549-C8-luc adenocarcinoma cells. These cells resulted in peri- and intra-bronchiolar tumors upon intrabronchial application and parenchymal tumors upon intravenous injection, respectively. Mice suffering from these lung tumors were treated with BC-819, complexed to branched polyethylenimine (PEI) and aerosolized to the mice once per week for a period of 10 weeks. Using this regimen, growth of i