REVIEW: Recent Developments in Bioprocessing of Recombinant Antibody Fragments

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Nevena Zelenovic¹, Lidija Filipovic², and Milica Popovic^3,a*

¹Center for Chemistry, Institute for Chemistry, Technology, and Metallurgy, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia

²Innovative Centre, Faculty of Chemistry, University of Belgrade, 11000 Belgrade, Serbia

³Department of Biochemistry, Faculty of Chemistry, University of Belgrade, 11000 Belgrade, Serbia

^* To whom correspondence should be addressed.

Received May 13, 2023; Revised July 12, 2023; Accepted August 18, 2023

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Biotechnological and biomedical applications of antibodies have been on a steady rise since the 1980s. As unique and highly specific bioreagents, monoclonal antibodies (mAbs) have been widely exploited and approved as therapeutic agents. However, the use of mAbs has limitations for therapeutic applications. Antibody fragments (AbFs) with preserved antigen-binding sites have a significant potential to overcome the disadvantages of conventional mAbs, such as heterogeneous tissue distribution after systemic administration, especially in solid tumors, and Fc-mediated bystander activation of the immune system. AbFs possess better biodistribution coefficient due to lower molecular weight. They preserve the functional features of mAbs, such as antigen specificity and binding, while at the same time, ensuring much better tissue penetration. An additional benefit of AbFs is the possibility of their production in bacterial and yeast cells due to the small size, more robust structure, and lack of posttranslational modifications. In this review, we described current approaches to the AbF production with recent examples of AbF synthesis in bacterial and yeast expression systems and methods for the production optimization.

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KEY WORDS: antibody fragments, bacterial expression, yeast expression, scFv, VHH

DOI: 10.1134/S0006297923090018

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