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Article Dans Une Revue mAbs Année : 2014

VEGF neutralizing aerosol therapy in primary pulmonary adenocarcinoma with K-ras activating-mutations

Nathalie Rabbe
  • Fonction : Auteur
Laurent Guilleminault
Flora Paul
  • Fonction : Auteur
Laurène Schlick
  • Fonction : Auteur
Michaël Duruisseaux
  • Fonction : Auteur
Marie Wislez
  • Fonction : Auteur
  • PersonId : 989590
Nathalie Heuzé-Vourc'H

Résumé

K-ras mutations promote angiogenesis in lung cancer and contribute to the drug resistance of cancer cells. It is not clear whether K-ras mutated adenocarcinomas are sensitive to anti-angiogenic therapy with monoclonal antibodies (mAbs) that target vascular endothelial growth factor (VEGF). Anti-angiogenic mAbs are usually delivered systemically, but only a small proportion reaches the lung after intravenous injection. We investigated the relevance of a non-invasive pulmonary route for the delivery of anti-VEGF mAbs in the mouse K-ras(LA1) model. We found that pulmonary delivery of these mAbs significantly reduced the number of tumor lesions and inhibited malignant progression. The antitumor effect involves the VEGFR2-dependent inhibition of blood vessel growth, which impairs tumor proliferation. Pharmacokinetic analysis of aerosolized anti-VEGF showed its low rate of passage into the bloodstream, suggesting that this delivery route is associated with reduced systemic side effects. Our findings highlight the value of the aerosol route for administration of anti-angiogenic mAbs in pulmonary adenocarcinoma with K-ras activating-mutations.

Dates et versions

hal-01769888 , version 1 (18-04-2018)

Identifiants

Citer

Virginie Herve, Nathalie Rabbe, Laurent Guilleminault, Flora Paul, Laurène Schlick, et al.. VEGF neutralizing aerosol therapy in primary pulmonary adenocarcinoma with K-ras activating-mutations. mAbs, 2014, 6 (6), pp.1638 - 1648. ⟨10.4161/mabs.34454⟩. ⟨hal-01769888⟩
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