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Isolation and preliminary characterization of a human ‘phage display’-derived antibody against neural adhesion molecule-1 antigen interfering with fibroblast growth factor receptor-1 binding

Isolation and preliminary characterization of a human ‘phage display’-derived antibody against... BACKGROUND:The NCAM or CD56 antigen is a cell surface glycoprotein belonging to the immunoglobulin super-family involved in cell-cell and cell-matrix adhesion. NCAM is also over-expressed in many tumour types and is considered a tumour associated antigen, even if its role and biological mechanisms implicated in tumour progression and metastasis have not yet to be elucidated. In particular, it is quite well documented the role of the interaction between the NCAM protein and the fibroblast growth factor receptor-1 in metastasis and invasion, especially in the ovarian cancer progression.OBJECTIVE:Here we describe the isolation and preliminary characterization of a novel human anti-NCAM single chain Fragment variable antibody able to specifically bind NCAM-expressing cells, including epithelial ovarian cancer cells.METHODS:The antibody was isolate by phage display selection and was characterized by ELISA, FACS analysis and SPR experiments. Interference in EOC migration was analyzed by scratch test.RESULTS:It binds a partially linear epitope lying in the membrane proximal region of two fibronectin-like domains with a dissociation constant of 3.43 × 10-8 M. Interestingly, it was shown to interfere with the NCAM-FGFR1 binding and to partially decrease migration of EOC cells.CONCLUSIONS:According to our knowledge, this is the first completely human antibody able to interfere with this newly individuated cancer mechanism. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Human Antibodies IOS Press

Isolation and preliminary characterization of a human ‘phage display’-derived antibody against neural adhesion molecule-1 antigen interfering with fibroblast growth factor receptor-1 binding

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Publisher
IOS Press
Copyright
Copyright © 2021 © 2021 – IOS Press. All rights reserved.
ISSN
1093-2607
eISSN
1875-869X
DOI
10.3233/HAB-200431
Publisher site
See Article on Publisher Site

Abstract

BACKGROUND:The NCAM or CD56 antigen is a cell surface glycoprotein belonging to the immunoglobulin super-family involved in cell-cell and cell-matrix adhesion. NCAM is also over-expressed in many tumour types and is considered a tumour associated antigen, even if its role and biological mechanisms implicated in tumour progression and metastasis have not yet to be elucidated. In particular, it is quite well documented the role of the interaction between the NCAM protein and the fibroblast growth factor receptor-1 in metastasis and invasion, especially in the ovarian cancer progression.OBJECTIVE:Here we describe the isolation and preliminary characterization of a novel human anti-NCAM single chain Fragment variable antibody able to specifically bind NCAM-expressing cells, including epithelial ovarian cancer cells.METHODS:The antibody was isolate by phage display selection and was characterized by ELISA, FACS analysis and SPR experiments. Interference in EOC migration was analyzed by scratch test.RESULTS:It binds a partially linear epitope lying in the membrane proximal region of two fibronectin-like domains with a dissociation constant of 3.43 × 10-8 M. Interestingly, it was shown to interfere with the NCAM-FGFR1 binding and to partially decrease migration of EOC cells.CONCLUSIONS:According to our knowledge, this is the first completely human antibody able to interfere with this newly individuated cancer mechanism.

Journal

Human AntibodiesIOS Press

Published: Mar 24, 2021

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