Understanding and controlling the molecular mechanisms of protein aggregation in mAb therapeutics

被引：15

作者：

Pang, Kuin Tian ^{[1
,5
]}

Yang, Yuan Sheng ^{[1
]}

Zhang, Wei ^{[1
]}

Ho, Ying Swan ^{[1
]}

Sormanni, Pietro ^{[2
]}

Michaels, Thomas C. T. ^{[3
,4
]}

Walsh, Ian ^{[1
]}

Chia, Sean ^{[1
]}

机构：

[1] ASTAR, Bioproc Technol Inst, Singapore, Singapore

[2] Univ Cambridge, Yusuf Hamied Dept Chem, Chem Hlth, Cambridge, England

[3] Swiss Fed Inst Technol, Inst Biochem, Dept Biol, Otto Stern Weg 3, CH-8093 Zurich, Switzerland

[4] Swiss Fed Inst Technol, Bringing Mat Life Initiat, Zurich, Switzerland

[5] Nanyang Technol Univ, Sch Chem Chem Engn & Biotechnol, Singapore, Singapore

来源：

BIOTECHNOLOGY ADVANCES | 2023年 / 67卷

基金：

英国医学研究理事会;

关键词：

Antibodies; Protein aggregation; Protein self-association; Developability; Chemical kinetics; MONOCLONAL-ANTIBODY AGGREGATION; NUCLEATED-POLYMERIZATION MODEL; COMPETING GROWTH; CONFORMATIONAL STABILITY; DRIVING FORCES; SINGLE-DOMAIN; IGG1; ANTIBODY; HIGH-PRESSURE; LOW PH; KINETICS;

D O I：

10.1016/j.biotechadv.2023.108192

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

In antibody development and manufacturing, protein aggregation is a common challenge that can lead to serious efficacy and safety issues. To mitigate this problem, it is important to investigate its molecular origins. This review discusses (1) our current molecular understanding and theoretical models of antibody aggregation, (2) how various stress conditions related to antibody upstream and downstream bioprocesses can trigger aggregation, and (3) current mitigation strategies employed towards inhibiting aggregation. We discuss the relevance of the aggregation phenomenon in the context of novel antibody modalities and highlight how in silico approaches can be exploited to mitigate it.

引用

页数：14

共 50 条

[31] Protein misfolding and aggregation in neurodegenerative diseases: a review of pathogeneses, novel detection strategies, and potential therapeutics [J].

Gandhi, Jason ;

Antonelli, Anthony C. ;

Afridi, Adil ;

Vatsia, Sohrab ;

Joshi, Gunjan ;

Romanov, Victor ;

Murray, Ian V. J. ;

Khan, Sardar Ali .

REVIEWS IN THE NEUROSCIENCES, 2019, 30 (04) :339-358

[32] Aggregation Mechanisms and Molecular Structures of Amyloid-β in Alzheimer's Disease [J].

Niu, Zheng ;

Gui, Xinrui ;

Feng, Shuang ;

Reif, Bernd .

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[33] Molecular mechanisms of spatial protein quality control [J].

Alberti, Simon .

PRION, 2012, 6 (05) :437-442

[34] Conformational Evolution of Molecular Signatures during Amyloidogenic Protein Aggregation [J].

Devitt, George ;

Rice, William ;

Crisford, Anna ;

Nandhakumar, Iris ;

Mudher, Amrit ;

Mahajan, Sumeet .

ACS CHEMICAL NEUROSCIENCE, 2019, 10 (11) :4593-4611

[35] N-glycan Analysis in Molecular Medicine: Innovator and Biosimilar Protein Therapeutics [J].

Borza, Beata ;

Hajba, Laszlo ;

Guttman, Andras .

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[36] Understanding the Effect of Secondary Structures and Aggregation on Human Protein Folding Class Evolution [J].

Tina Begum ;

Tapash Chandra Ghosh .

Journal of Molecular Evolution, 2010, 71 :60-69

[37] Understanding the Effect of Secondary Structures and Aggregation on Human Protein Folding Class Evolution [J].

Begum, Tina ;

Ghosh, Tapash Chandra .

JOURNAL OF MOLECULAR EVOLUTION, 2010, 71 (01) :60-69

[38] Protein-protein interactions controlling interfacial aggregation of rhIL-1ra are not described by simple colloid models [J].

Sorret, Lea L. ;

DeWinter, Madison A. ;

Schwartz, Daniel K. ;

Randolph, Theodore W. .

PROTEIN SCIENCE, 2018, 27 (07) :1191-1204

[39] Competitive inhibition reaction mechanisms for the two-step model of protein aggregation [J].

Whidden, Mark ;

Ho, Allison ;

Ivanova, Magdalena I. ;

Schnell, Santiago .

BIOPHYSICAL CHEMISTRY, 2014, 193 :9-19

[40] Molecular chaperones antagonize proteotoxicity by differentially modulating protein aggregation pathways [J].

Douglas, Peter M. ;

Summers, Daniel W. ;

Cyr, Douglas M. .

PRION, 2009, 3 (02) :51-58

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