caa a22 4500 445312033 CHVBK 20180317142633.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s11095-011-0442-5 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0442-5 The Airways, a Novel Route for Delivering Monoclonal Antibodies to Treat Lung Tumors [Elektronische Daten] [Agnès Maillet, Laurent Guilleminault, Etienne Lemarié, Stéphanie Lerondel, Nicolas Azzopardi, Jérôme Montharu, Nicolas Congy-Jolivet, Pascale Reverdiau, Brigitte Legrain, Christelle Parent, Dominique-Henri Douvin, José Hureaux, Yves Courty, Michèle De Monte, Patrice Diot, Gilles Paintaud, Alain Le Pape, Hervé Watier, Nathalie Heuzé-Vourc'h] ABSTRACT: Purpose: Lung cancer is the leading cause of cancer-related death worldwide. The efficacy of current systemic treatments is limited, with major side effects and only modest survival improvements. Aerosols routinely used to deliver drugs into the lung for treating infectious and inflammatory lung diseases have never been used to deliver monoclonal antibodies to treat lung cancer. We have shown that cetuximab, a chimeric anticancer anti-EGFR mAb, is suitable for airway delivery as it resists the physical constraints of aerosolization, and have evaluated the aerosol delivery of cetuximab in vivo. Methods: We developed an animal model of lung tumor sensitive to cetuximab by injecting Balb/c Nude mice intratracheally with A431 cells plus 10mM EDTA and analyzed the distribution, pharmacokinetics and antitumor efficacy of cetuximab aerosolized into the respiratory tract. Results: Aerosolized IgG accumulated durably in the lungs and the tumor, but passed poorly and slowly into the systemic circulation. Aerosolized cetuximab also limited the growth of the mouse tumor. Thus, administering anticancer mAbs via the airways is effective and may limit systemic side effects. Conclusion: Delivery of aerosolized-mAbs via the airways deserves further evaluation for treating lung cancers. Springer Science+Business Media, LLC, 2011 aerosols nationallicence antibodies nationallicence carcinoma nationallicence monoclonal nationallicence non-small-cell lung nationallicence Maillet Agnès INSERM U618, Université François Rabelais de Tours, Tours, France aut Guilleminault Laurent INSERM U618, Université François Rabelais de Tours, Tours, France aut Lemarié Etienne INSERM U618, Université François Rabelais de Tours, Tours, France aut Lerondel Stéphanie TAAM-CIPA UPS44, Orléans, France aut Azzopardi Nicolas UMR6239 GICC, CHRU de Tours, Tours, France aut Montharu Jérôme PPF « Animaleries », Faculté de Médecine, Tours, France aut Congy-Jolivet Nicolas UMR6239 GICC, CHRU de Tours, Tours, France aut Reverdiau Pascale INSERM U618, Université François Rabelais de Tours, Tours, France aut Legrain Brigitte Laboratoires Novaxia, Saint Laurent Nouan, France aut Parent Christelle INSERM U618, Université François Rabelais de Tours, Tours, France aut Douvin Dominique-Henri Laboratoires Novaxia, Saint Laurent Nouan, France aut Hureaux José CHU d'Angers Service de Pneumologie, Angers, France aut Courty Yves INSERM U618, Université François Rabelais de Tours, Tours, France aut De Monte Michèle INSERM U618, Université François Rabelais de Tours, Tours, France aut Diot Patrice INSERM U618, Université François Rabelais de Tours, Tours, France aut Paintaud Gilles UMR6239 GICC, CHRU de Tours, Tours, France aut Le Pape Alain INSERM U618, Université François Rabelais de Tours, Tours, France aut Watier Hervé UMR6239 GICC, CHRU de Tours, Tours, France aut Heuzé-Vourc'h Nathalie INSERM U618, Université François Rabelais de Tours, Tours, France aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2147-2156 0724-8741 28:9<2147 2011 28 11095 https://doi.org/10.1007/s11095-011-0442-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0442-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Maillet Agnès INSERM U618, Université François Rabelais de Tours, Tours, France aut NATIONALLICENCE 700 1- Guilleminault Laurent INSERM U618, Université François Rabelais de Tours, Tours, France aut NATIONALLICENCE 700 1- Lemarié Etienne INSERM U618, Université François Rabelais de Tours, Tours, France aut NATIONALLICENCE 700 1- Lerondel Stéphanie TAAM-CIPA UPS44, Orléans, France aut NATIONALLICENCE 700 1- Azzopardi Nicolas UMR6239 GICC, CHRU de Tours, Tours, France aut NATIONALLICENCE 700 1- Montharu Jérôme PPF « Animaleries », Faculté de Médecine, Tours, France aut NATIONALLICENCE 700 1- Congy-Jolivet Nicolas UMR6239 GICC, CHRU de Tours, Tours, France aut NATIONALLICENCE 700 1- Reverdiau Pascale INSERM U618, Université François Rabelais de Tours, Tours, France aut NATIONALLICENCE 700 1- Legrain Brigitte Laboratoires Novaxia, Saint Laurent Nouan, France aut NATIONALLICENCE 700 1- Parent Christelle INSERM U618, Université François Rabelais de Tours, Tours, France aut NATIONALLICENCE 700 1- Douvin Dominique-Henri Laboratoires Novaxia, Saint Laurent Nouan, France aut NATIONALLICENCE 700 1- Hureaux José CHU d'Angers Service de Pneumologie, Angers, France aut NATIONALLICENCE 700 1- Courty Yves INSERM U618, Université François Rabelais de Tours, Tours, France aut NATIONALLICENCE 700 1- De Monte Michèle INSERM U618, Université François Rabelais de Tours, Tours, France aut NATIONALLICENCE 700 1- Diot Patrice INSERM U618, Université François Rabelais de Tours, Tours, France aut NATIONALLICENCE 700 1- Paintaud Gilles UMR6239 GICC, CHRU de Tours, Tours, France aut NATIONALLICENCE 700 1- Le Pape Alain INSERM U618, Université François Rabelais de Tours, Tours, France aut NATIONALLICENCE 700 1- Watier Hervé UMR6239 GICC, CHRU de Tours, Tours, France aut NATIONALLICENCE 700 1- Heuzé-Vourc'h Nathalie INSERM U618, Université François Rabelais de Tours, Tours, France aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2147-2156 0724-8741 28:9<2147 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer