Antibody fragments without the Fc region are attracting attention in the pharmaceutical industry due to their high ability to penetrate solid tissues, cost-effective expression using microbial expression systems, and distinctive modes of action compared to those of full-size antibodies. Based on these characteristics, several antibody fragment agents have been approved. However, developing platform engineering methodologies to accelerate their development is important. In this review, we summarize and discuss protein engineering strategies for preparing therapeutic antibody fragments composed of antibody variable domains. Three (introduction of high-solubility tag systems, complementarity-determining region grafting, and domain arrangements) and two (introduction of purification tag systems and mutagenesis studies for protein L- or protein A-binding) protein engineering strategies have been reported for the cultivation and purification processes, respectively. Fusion tags might negatively impact molecular folding, function, immunogenicity, and final yield. If the production behavior of antibody fragments is not improved through complementarity-determining region grafting, domain arrangements, or human sequence-based mutagenesis, using additional fusion tag systems should be considered, with careful attention to the points described above. This summarized knowledge regarding protein engineering strategies for effectively producing antibody fragments will further accelerate therapeutic antibody fragment development.
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September 2023
Review Article|
September 07 2023
Protein engineering of antibody fragments for pharmaceutical production
Special Collection:
Materials and Technologies for Bioimaging and Biosensing
Atsushi Kuwahara;
Atsushi Kuwahara
(Writing – original draft)
1
Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology
, Tokyo 184-8588, Japan
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Kazunori Ikebukuro
;
Kazunori Ikebukuro
(Writing – review & editing)
1
Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology
, Tokyo 184-8588, Japan
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Ryutaro Asano
Ryutaro Asano
a)
(Supervision, Writing – review & editing)
1
Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology
, Tokyo 184-8588, Japan
2
Institute of Global Innovation Research, Tokyo University of Agriculture and Technology
, Tokyo 183-8509, Japan
a)Author to whom correspondence should be addressed: ryutaroa@cc.tuat.ac.jp. Tel.:/Fax: 81-42-388-7512
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a)Author to whom correspondence should be addressed: ryutaroa@cc.tuat.ac.jp. Tel.:/Fax: 81-42-388-7512
Appl. Phys. Rev. 10, 031311 (2023)
Article history
Received:
May 14 2023
Accepted:
August 02 2023
Connected Content
A companion article has been published:
Protein engineering strategies contribute efficient production of therapeutic antibody fragments
Citation
Atsushi Kuwahara, Kazunori Ikebukuro, Ryutaro Asano; Protein engineering of antibody fragments for pharmaceutical production. Appl. Phys. Rev. 1 September 2023; 10 (3): 031311. https://doi.org/10.1063/5.0158032
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