Herceptin Research Today is a free monthly online journal that collates and summarizes the latest research about Herceptin, including details on side-effects, breast cancer, treatment, therapy.

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

Belimezi MM, Papanastassiou D, Merkouri E, Baxevanis CN, Mamalaki A

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

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.

Published 24 May 2006 in Cancer Immunol Immunother, 55(9): 1091-9.
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