Aerodynamical, immunological and pharmacological properties of the anticancer antibody cetuximab

Type Article
Date 2008-06
Language English
Author(s) Maillet A1, Congy Jolivet N2, 3, Le Guellec S4, Vecellio L1, Hamard S1, Courty Y1, Courtois Anthony5, 6, Gauthier F1, Diot P1, 3, Thibault G2, 3, Lemarie E1, 3, Heuze Vourc' h N1, 7
Affiliation(s) 1 : Univ Tours, U618, Tours, France.
2 : Univ Tours, UPRES EA 3853, IPGA, Tours, France.
3 : CHRU Tours, F-37000 Tours, France.
4 : DTF, Atomisor, F-42003 St Etienne, France.
5 : Univ Bretagne Occidentale, Lab Therapie Cellulaire & Immunobiol Canc, CHU Morvan Brest, Brest, France.
6 : IFREMER, Lab Biotechnol & Mol Marines, Plouzane, France.
7 : Fac Med, INSERM, U618, F-37032 Tours, France.
Source Pharmaceutical Research (0724-8741) (Springer), 2008-06 , Vol. 25 , N. 6 , P. 1318-1326
DOI 10.1007/s11095-007-9481-3
WOS© Times Cited 30
Keyword(s) Nebulizer, Lung cancer, Cetuximab, Anticancer antibody, Aggregation, Aerosol
Abstract Purpose. Despite an increasing interest in the use of inhalation for local delivery of molecules for respiratory diseases and systemic disorders, methods to deliver therapy through air-ways has received little attention for lung cancer treatment. However, inhalation of anticancer drugs is an attractive alternative route to systemic administration which results in limited concentration of the medication in the lungs, and triggers whole-body toxicity. In this study, we investigated the feasibility of nebulization for therapeutic antibodies, a new class of fully-approved anticancer drugs in oncology medicine.

Materials and methods. Cetuximab, a chimeric IgG1 targeting the epidermal growth factor receptor (EGER), was nebulized using three types of delivery devices: a jet nebulizer PARI LC+(R), a mesh nebulizer AeronebPro (R) and an ultrasonic nebulizer SYST'AM (R) LS290. Aerosol size distribution was measured using a cascade impactor and aerosol droplets were observed under optical microscopy. The immunological and pharmacological properties of cetuximab were evaluated following nebulization using A431 cells.

Results. The aerosol particle clouds generated with the three nebulizers displayed similar aerodynamical characteristics, but the IgG formed aggregates in liquid phase following nebulization with both the jet and ultrasonic devices. Flow cytometry analyses and assays of EGFR-phosphorylation and cell growth inhibitions on A431 demonstrated that both the mesh and the jet nebulizers preserved the binding affinity to EGER and the inhibitory activities of cetuximab.

Conclusions. Altogether, our results indicate that cetuximab resists the physical constraints of nebulization, Thus, airway delivery represents a promising alternative to systemic administration for local delivery of therapeutic antibodies in lung cancer treatment.
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Maillet A, Congy Jolivet N, Le Guellec S, Vecellio L, Hamard S, Courty Y, Courtois Anthony, Gauthier F, Diot P, Thibault G, Lemarie E, Heuze Vourc' h N (2008). Aerodynamical, immunological and pharmacological properties of the anticancer antibody cetuximab. Pharmaceutical Research, 25(6), 1318-1326. Publisher's official version : https://doi.org/10.1007/s11095-007-9481-3 , Open Access version : https://archimer.ifremer.fr/doc/00000/4201/