Facile and Rapid Glycosylation Monitoring of Therapeutic Antibodies Through Intact Protein Analysis

다국어 초록 (Multilingual Abstract)

The therapeutic antibody drug market has experienced explosive growth as mAbs become the main therapeutic modality for a variety of diseases. Characterization of glycosylation that directly affects the efficacy and safety of therapeutic monoclonal antibodies (mAbs) is critical for therapeutics development, bioprocess system optimization, lot release, and compa- rability evaluation. The LC/MS approach has been widely used to structurally characterize mAbs, and recently attempts have been made to obtain comprehensive information on the primary structure and post-translational modifications (PTMs) of mAbs through intact protein analysis. In this study, we performed state-of-the-art LC/MS based intact protein analysis to readily iden- tify and characterize glycoforms of various mAbs. Different glycoforms of mAbs produced in different expression cell lines includ- ing CHO, SP2/0 and HEK cells were monitored and compared. In addition, the comparability of protein molecular weight, glycoform pattern, and relative abundances of glycoforms between the commercialized trastuzumab biosimilar and the original product was determined in detail using the given platform. Intact mAb analysis allowed us to gain insight into the overall mAb structure, including the complexity and diversity of glycosylation. Furthermore, our analytical platform with high reproducibility is expected to be widely used for biopharmaceutical characterization required at all stages of drug development and manufacturing.

참고문헌 (Reference)

1 Singh, S., 13 : 85-, 2018

2 Kellie, J. F., 32 : 1886-, 2021

3 Beck, A., 85 : 715-, 2013

4 Jiang, X. R., 10 : 101-, 2011

5 Liu, H., 97 : 2426-, 2008

6 Zheng, K., 3 : 568-, 2011

7 Wright, A., 15 : 26-, 1997

8 Jefferis, R, 8 : 226-, 2009

9 Chung, A. W., 28 : 2523-, 2014

10 Beck, A., 9 : 482-, 2008

11 Vidarsson, G., 5 : 520-, 2014

12 Tsuda, E., 188 : 405-, 1990

13 Lawson, E. Q., 220 : 572-, 1983

14 Duivelshof, B. L., 1089 : 1-, 2019

15 Ferrara, C., 108 : 12669-, 2011

16 Zhang, Z., 28 : 147-, 2009

17 Oh, M. J., 8 : 711-, 2016

18 Hua, S., 68 : 18-, 2015

19 Grilo, A. L., 37 : 9-, 2019

20 Zhang, P. Q., 21 : 740-, 2016

21 Dotz, V., 73 : 1-, 2015

22 Zhu, W., 20 : 270-, 2021

23 Fussl, F., 92 : 5431-, 2020

24 Wang, G. B., 89 : 4793-, 2017

25 Rosati, S., 9 : 967-, 2014

26 Oh, M. J., "in press" 2021