[The hinge region of therapeutic antibodies: major importance of a short sequence].
La région charnière des anticorps thérapeutiques - L’importance capitale d’une courte séquence.
Journal
Medecine sciences : M/S
ISSN: 1958-5381
Titre abrégé: Med Sci (Paris)
Pays: France
ID NLM: 8710980
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
entrez:
7
1
2020
pubmed:
7
1
2020
medline:
23
6
2020
Statut:
ppublish
Résumé
The hinge region is a short sequence of the heavy chains (H) of antibodies linking the Fab (Fragment antigen binding) region to the Fc (Fragment crystallisable) region. The functional properties of the four IgG subclasses partly result from the sequence differences of their hinge regions as some amino acids of the lower hinge region are located within or in the close vicinity of the C1q and FcγR binding sites on the IgG H chains. In addition, the hinge is susceptible to proteolytic cleavage by many proteases present in tumor and/or inflammatory microenvironment capable of affecting functional responses. Thus, an optimal format of the hinge region remains a major challenge for the development of new therapeutic antibodies. La région charnière des anticorps thérapeutiques - L’importance capitale d’une courte séquence. La région charnière est une courte séquence des chaînes lourdes (H) d’anticorps liant le Fab (fragment antigen binding) au Fc (fragment crystallisable). Les propriétés fonctionnelles des quatre sous-classes d’immunoglobulines d’isotype G (IgG) résultent en partie des différences de séquence de leurs régions charnières. En effet, certains acides aminés de la partie C-terminale de ces régions charnières (« partie basse ») sont situés au sein ou à proximité des sites de liaison de la molécule C1q de la voie classique du complément et des récepteurs pour la région Fc des IgG (RFcγ) sur les chaînes H d’IgG. Les régions charnières sont également sensibles au clivage protéolytique par de nombreuses protéases du microenvironnement tumoral et/ou inflammatoire pouvant altérer les réponses fonctionnelles. Le format optimal de la charnière reste donc un défi majeur pour le développement de nouveaux anticorps thérapeutiques.
Autres résumés
Type: Publisher
(fre)
La région charnière des anticorps thérapeutiques - L’importance capitale d’une courte séquence.
Identifiants
pubmed: 31903923
doi: 10.1051/medsci/2019218
pii: msc190006
doi:
Substances chimiques
Antibodies, Monoclonal
0
Immunoglobulin Fab Fragments
0
Immunoglobulin Fc Fragments
0
Immunoglobulin G
0
Peptide Hydrolases
EC 3.4.-
Types de publication
Journal Article
Review
Langues
fre
Sous-ensembles de citation
IM
Pagination
1098-1105Informations de copyright
© 2019 médecine/sciences – Inserm.
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