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LC-MS analysis of sintilimab as an anti-PD-1 therapeutic mab for its improved hinge stability study
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Chuan-fei YU1, Xing-jun CAO2, Wen-bo WANG1, Hai-qing NI2, Amy Y GUO2, Lan WANG1, *
Acta Pharmaceutica Sinica | 2019, 54(1) : 122 - 129
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Acta Pharmaceutica Sinica | 2019, 54(1): 122-129
• ORIGINAL ARTICLES •
LC-MS analysis of sintilimab as an anti-PD-1 therapeutic mab for its improved hinge stability study
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Chuan-fei YU1, Xing-jun CAO2, Wen-bo WANG1, Hai-qing NI2, Amy Y GUO2, Lan WANG1, *
Affiliations
  • 1. National Institutes for Food and Drug Control, Beijing 102629, China
  • 2. Innovent Biologics Suzhou Co. Ltd, Suzhou 215123, China
Published: 2019-01-12 doi: 10.16438/j.0513-4870.2018-0574
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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.

IgG4  /  Fab-arm exchange  /  LC-MS  /  PD-1  /  sintilimab
Chuan-fei YU, Xing-jun CAO, Wen-bo WANG, Hai-qing NI, Amy Y GUO, Lan WANG. LC-MS analysis of sintilimab as an anti-PD-1 therapeutic mab for its improved hinge stability study[J]. Acta Pharmaceutica Sinica, 2019 , 54 (1) : 122 -129 . DOI: 10.16438/j.0513-4870.2018-0574
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Article Info
doi: 10.16438/j.0513-4870.2018-0574
  • Receive Date：2018-06-21
  • Online Date：2026-01-26
  • Published：2019-01-12
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  • Received：2018-06-21
  • Revised：2018-08-03
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    1. National Institutes for Food and Drug Control, Beijing 102629, China
    2. Innovent Biologics Suzhou Co. Ltd, Suzhou 215123, China
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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