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LC-MS analysis of sintilimab as an anti-PD-1 therapeutic mab for its improved hinge stability study / 药学学报
Acta Pharmaceutica Sinica ; (12): 122-129, 2019.
Article in Chinese | WPRIM | ID: wpr-778669
ABSTRACT
Monoclonal antibodies (mAbs) have been widely used as therapeutic drugs for treating diseases such as cancers and auto-immune diseases. When using an IgG4 isotype, one of the challenges is the instability of its hinge which is prone to Fab-arm exchange (FAE). The hinge sequence of a wild type IgG4 is -CPSC-, however, a single point mutation S228P from -CPSC- to -CPPC- can effectively diminish FAE, thereby improving hinge stability of the IgG4 molecule. Sintilimab is the fully human anti-PD-1 monoclonal antibody designed and developed for immuno-oncology, in which serine 228 in the hinge was engineered to proline to mitigate FAE. In this study, LC-MS is used to study hinge stability of sintilimab in both in vitro (PBS and human serum) and in vivo (SCID mouse) studies. The studies demonstrate that LC-MS is a fast and simple way to monitor for the occurrence of FAE in vitro and in vivo, and FAE can be eliminated by antibody engineering with a single point mutation.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Acta Pharmaceutica Sinica Year: 2019 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Acta Pharmaceutica Sinica Year: 2019 Type: Article