title: Glycosylation profiles determine extravasation and disease-targeting properties of armed antibodies.
abstract: The ability of antibodies to extravasate out of blood vessels is critical for therapeutic activity, because molecular targets for most diseases are located outside of the endothelial lining. By performing detailed biodistribution studies with a novel IL9-armed cancer-specific antibody, we identified a clear correlation between N-linked glycan structures and tumor-targeting efficiencies. Site-specific glycan analysis provided a detailed view of the glycan microheterogeneity present on the IL9 portion of the recombinant protein. Nonsialylated glycan structures have a negative impact on disease-homing activity, highlighting the importance of glycosylation control and characterization during process development.
authors: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, and.
authors: Dario
authors: D
authors: Venetz
authors: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, and.
authors: Christian
authors: C
authors: Hess
authors: Institute of Microbiology, Department of Biology, Swiss Federal Institute of Technology, CH-8093 Zürich, Switzerland.
authors: Chia-wei
authors: CW
authors: Lin
authors: Institute of Microbiology, Department of Biology, Swiss Federal Institute of Technology, CH-8093 Zürich, Switzerland.
authors: Markus
authors: M
authors: Aebi
authors: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, and neri@pharma.ethz.ch.
authors: Dario
authors: D
authors: Neri
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D001483:Base Sequence; D017931:DNA Primers; D005119:Extravasation of Diagnostic and Therapeutic Materials; D005260:Female; D006031:Glycosylation; D051379:Mice; D016133:Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000906:Antibodies; D017931:DNA Primers
keywords: armed antibody; glycosylation; interleukin-9; site-specific glycan analysis; tumor targeting
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