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01-09-2006 | Original Article

Growth inhibition of breast cancer cell lines overexpressing Her2/neu by a novel internalized fully human Fab antibody fragment

Authors: Maria M. Belimezi, Danai Papanastassiou, Efrossini Merkouri, Constantin N. Baxevanis, Avgi Mamalaki

Published in: Cancer Immunology, Immunotherapy | Issue 9/2006

Abstract

The Her2/neu oncogene is overexpressed in various human cancers of epithelial origin and is associated with increased metastatic potential and poor prognosis. Blocking the Her2/neu signalling has been the focus of most therapeutic approaches. In this paper, the Her2/neu extracellular domain expressed in soluble form in yeast Pichia pastoris was used in order to isolate a fully human Fab fragment from a combinatorial Fab phage display library, derived from invaded lymph nodes of a breast cancer patient. The isolated fully human Fab63 binds specifically the native Her2/neu receptor and competes with Herceptin for binding to soluble Her2/neu receptor. In Her2/neu overexpressing cancer cells, Fab63 is rapidly internalized and has significant antiproliferative effects, where ligand-independent mechanisms dominate signal induction. Moreover, in the presence of the ligand heregulin, growth inhibition was also detected by Fab63. The human Fab63 is a non-immunogenic agent with unique properties that can be applied in diagnosis and cancer therapy, with great potential for further manipulation towards the generation of an effective anticancer molecule.

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Title: Growth inhibition of breast cancer cell lines overexpressing Her2/neu by a novel internalized fully human Fab antibody fragment
Authors: Maria M. Belimezi
Danai Papanastassiou
Efrossini Merkouri
Constantin N. Baxevanis
Avgi Mamalaki
Publication date: 01-09-2006
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 9/2006
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-005-0100-z

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