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Cancer Immunol Immunother. 2006 Sep;55(9):1091-9. Epub 2005 Nov 26.

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

Author information

1
Laboratory of Molecular Biology and Immunobiotechnology, Department of Biochemistry, Hellenic Pasteur Institute, 127 Vas. Sofias Ave., 11521 Athens, Greece.

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.

PMID:
16311733
DOI:
10.1007/s00262-005-0100-z
[Indexed for MEDLINE]

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