title: The airways, a novel route for delivering monoclonal antibodies to treat lung tumors.
abstract: OBJECTIVE
  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 10 mM 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.
  
  
  CONCLUSIONS
  Delivery of aerosolized-mAbs via the airways deserves further evaluation for treating lung cancers.
authors.affiliation: INSERM U618, Université François Rabelais de Tours, Tours, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Maillet
authors.forename: Laurent
authors.initials: L
authors.lastname: Guilleminault
authors.forename: Etienne
authors.initials: E
authors.lastname: Lemarié
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lerondel
authors.forename: Nicolas
authors.initials: N
authors.lastname: Azzopardi
authors.forename: Jérôme
authors.initials: J
authors.lastname: Montharu
authors.forename: Nicolas
authors.initials: N
authors.lastname: Congy-Jolivet
authors.forename: Pascale
authors.initials: P
authors.lastname: Reverdiau
authors.forename: Brigitte
authors.initials: B
authors.lastname: Legrain
authors.forename: Christelle
authors.initials: C
authors.lastname: Parent
authors.forename: Dominique-Henri
authors.initials: DH
authors.lastname: Douvin
authors.forename: José
authors.initials: J
authors.lastname: Hureaux
authors.forename: Yves
authors.initials: Y
authors.lastname: Courty
authors.forename: Michèle
authors.initials: M
authors.lastname: De Monte
authors.forename: Patrice
authors.initials: P
authors.lastname: Diot
authors.forename: Gilles
authors.initials: G
authors.lastname: Paintaud
authors.forename: Alain
authors.initials: A
authors.lastname: Le Pape
authors.forename: Hervé
authors.initials: H
authors.lastname: Watier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Heuzé-Vourc'h
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015153:Blotting, Western; D045744:Cell Line, Tumor; D000068818:Cetuximab; D004355:Drug Stability; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000336:Aerosols; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068818:Cetuximab