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.
FGFR1
NCAM
epithelial ovarian cancer
phage display
single-chain variable fragment
Journal
Human antibodies
ISSN: 1875-869X
Titre abrégé: Hum Antibodies
Pays: Netherlands
ID NLM: 9711270
Informations de publication
Date de publication:
2021
2021
Historique:
pubmed:
10
11
2020
medline:
10
9
2021
entrez:
9
11
2020
Statut:
ppublish
Résumé
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. 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. 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. 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. According to our knowledge, this is the first completely human antibody able to interfere with this newly individuated cancer mechanism.
Sections du résumé
BACKGROUND
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
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
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
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
CONCLUSIONS
According to our knowledge, this is the first completely human antibody able to interfere with this newly individuated cancer mechanism.
Identifiants
pubmed: 33164927
pii: HAB200431
doi: 10.3233/HAB-200431
doi:
Substances chimiques
Immunoglobulins
0
Neural Cell Adhesion Molecules
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM