The Airways, a Novel Route for Delivering Monoclonal Antibodies to Treat Lung Tumors

• DOI: 10.1007/s11095-011-0442-5
• Publication Date: 2011-04-13T15:19:38Z
• Authors: Agnès Maillet; Laurent Guillemin...; Etienne Lemarié; Stéphanie Lerondel; Nicolas Azzopardi; Jérôme Montharu; Nicolas Congy-Jol...; Pascale Reverdiau; Brigitte Legrain; Christelle Parent; Dominique-Henri D...; José Hureaux; Yves Courty; Michèle De Monte; Patrice Diot; Gilles Paintaud; Alain Le Pape; Hervé Watier; Nathalie Heuzé-Vo...
• Keywords: 0301 basic medicine; [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication; Lung Neoplasms; Blotting, Western; Cetuximab; Mice, Nude; [SDV.CAN]Life Sciences [q-bio]/Cancer; Antineoplastic Agents; Enzyme-Linked Immunosorbent Assay; Antibodies, Monoclonal, Humanized; Mice; 03 medical and health sciences; [SDV.CAN] Life Sciences [q-bio]/Cancer; [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication; Drug Stability; Cell Line, Tumor; Administration, Inhalation; Animals; Tissue Distribution; Lung; Aerosols; Mice, Inbred BALB C; Antibodies, Monoclonal; Xenograft Model Antitumor Assays; 3. Good health; Injections, Intravenous; Female

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.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.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.Delivery of aerosolized-mAbs via the airways deserves further evaluation for treating lung cancers.