Application of fucosylation inhibitors for production of afucosylated antibody.
Biotechnol Prog
; 40(3): e3438, 2024.
Article
in En
| MEDLINE
| ID: mdl-38415431
ABSTRACT
Fucosylation is an important quality attribute for therapeutic antibodies. Afucosylated antibodies exhibit higher therapeutic efficacies than their fucosylated counterparts through antibody-dependent cellular cytotoxicity (ADCC) mechanism. Since higher potency is beneficial in reducing dose or duration of the treatment, afucosylated antibodies have attracted a great deal of interest in biotherapeutics development. In this study, novel small molecules GDP-D-Rhamnose and its derivatives (Ac-GDP-D-Rhamnose and rhamnose sodium phosphate) were synthesized to inhibit the enzyme in the GDP-fucose synthesis pathway. Addition of these compounds into cell culture increased antibody afucosylation levels in a dose-dependent manner and had no significant impact on other protein quality attributes. A novel and effective mechanism to generate afucosylated antibody is demonstrated for biologics discovery, analytical method development, process development, and other applications.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cricetulus
/
Fucose
Limits:
Animals
/
Humans
Language:
En
Journal:
Biotechnol Prog
/
Biotechnol. pog
/
Biotechnology progress
Journal subject:
BIOTECNOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Estados Unidos