Background And Objective: The application of immunotherapy, especially in terms of recombinant monoclonal antibodies (mAbs), is a revolution in the pharmaceutical industry field. Glycosylation plays an essential role in the structures and functions of mAbs, which must be carefully monitored and designed throughout their entire lifespan to ensure safety and efficacy. This review aimed to summarize the current status of the glycoengineering of mAbs for providing reference for the pharmaceutical industry. The application of glycoengineering of mAbs in cancer therapy will also be discussed in this article.
Methods: We searched the PubMed/MEDLINE database to identify studies published between 1970 and 2023 that investigated glycoengineering of recombinant mAbs and its applications. The major findings of these studies were summarized.
Key Content And Findings: This article reviews the relationship between glycosylation profiles and antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), shelf-life, and other properties of mAbs. Furthermore, the rational design of glycosylation profiles provides solutions to the unmet needs of new drug development and biosimilar manufacturers. This review also emphatically describes various feasible strategies to optimize the glycosylation pattern in biomanufacturing reported in recent years, especially the approaches of combinatory glycoengineering explored in this field. Finally, we share examples of glycoengineering of mAbs applied in cancer therapy.
Conclusions: Glycan modifications have been achieved through genetic and metabolic glycoengineering. A better understanding of the interplay between cells and the exogenous environment help the combinatorial strategy for glycoengineering in precise control mode. Furthermore, new high-tech approaches for glycoengineering are leading biological engineering and biotherapeutics to a new stage.
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http://dx.doi.org/10.21037/tcr-23-1371 | DOI Listing |
Blood Adv
December 2024
Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Haemolytic disease of the foetus and newborn (HDFN) due to Rhesus D (RhD) antigen mismatch between the mother and foetus has been a significant cause of neonatal jaundice, recurrent miscarriage and stillbirth throughout history. Anti-RhD prophylaxis using polyclonal immunoglobulin G (RhD-pIgG) derived from the plasma of RhD-negative donors immunised with RhD-positive red blood cells (RBCs), has reduced the incidence of HDFN, but this approach is currently restricted to developed countries. Monoclonal antibodies (mAbs) offer a promising alternative to address this pressing need, but prior attempts to develop effective anti-RhD mAbs have failed, in some cases due to differences in fucosylation patterns between mAbs produced in cell lines and RhD-pIgG.
View Article and Find Full Text PDFMAbs
November 2024
Lek d.d. Part of Sandoz, Biopharma Technical Development, Ljubljana, Slovenia.
Development of novel therapeutic proteins and biosimilars requires a thorough understanding of the relationship between their structure and function. Particularly, how IgG glycosylation affects its effector functions is a point increasingly underscored in guidelines by the World Health Organization and regulatory agencies. Our results show that just a 1% decrease in Fc fucosylation can lead to a more than 25% increase in antibody-dependent cell-mediated cytotoxicity.
View Article and Find Full Text PDFFront Immunol
November 2024
Institute of Plant Biotechnology and Cell Biology, Department of Applied Genetics and Cell Biology, BOKU University, Vienna, Austria.
Despite the unique advantages of IgG3 over other IgG subclasses, such as mediating enhanced effector functions and increased flexibility in antigen binding due to a long hinge region, the therapeutic potential of IgG3 remains largely unexplored. This may be attributed to difficulties in recombinant expression and the reduced plasma half-life of most IgG3 allotypes. Here, we report plant expression of two SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) that exhibit high (P5C3) and low (H4) antigen binding.
View Article and Find Full Text PDFCommun Chem
September 2024
Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands.
Monoclonal antibody (mAb) glycoengineering has the potential to improve the efficacy of biopharmaceuticals by fine-tuning specific biological properties. Glycosylation analysis is key to monitoring the glycoengineering process. Various mass spectrometry (MS)-based methods are available to characterize mAb glycosylation at different structural levels, but comprehensive analysis is typically time-consuming and costly.
View Article and Find Full Text PDFPlant Biotechnol J
November 2024
Department of Life Science, Sogang University, Seoul, South Korea.
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