title: Aerosolized BC-819 inhibits primary but not secondary lung cancer growth.
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 intrabronchially induced lung tumors was significantly inhibited (p = 0.01), whereas no effect could be observed in mice suffering from lung metastasis. In summary, we suggest that aerosolized PEI/BC-819 is capable of reducing growth only in tumors arising from the luminal part of the airways and are therefore directly accessible for inhaled BC-819.
authors.affiliation: Department of Pediatrics, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Hasenpusch
authors.forename: Corinna
authors.initials: C
authors.lastname: Pfeifer
authors.forename: Manish Kumar
authors.initials: MK
authors.lastname: Aneja
authors.forename: Kai
authors.initials: K
authors.lastname: Wagner
authors.forename: Dietrich
authors.initials: D
authors.lastname: Reinhardt
authors.forename: Michal
authors.initials: M
authors.lastname: Gilon
authors.forename: Patricia
authors.initials: P
authors.lastname: Ohana
authors.forename: Avraham
authors.initials: A
authors.lastname: Hochberg
authors.forename: Carsten
authors.initials: C
authors.lastname: Rudolph
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000556:secondary*; D051379:Mice; D009857:Oncogenes / Q000235:genetics; D010957:Plasmids / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D011094:Polyethyleneimine / Q000737:chemistry
chemical_list: D000336:Aerosols; D011094:Polyethyleneimine