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REVIEW article
Front. Immunol.
Sec. B Cell Biology
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1469329
This article is part of the Research Topic The Development, and Applications, of in vitro Immunological Display Technologies View all articles
Advancements in Mammalian Display Technology for Therapeutic Antibody Development and Beyond: Current Landscape, Challenges, and Future Prospects
Provisionally accepted
Peter Slavny
1,2*
Manjunath Hegde
3*
Achim Doerner
4
Kothai Parthiban
2
John McCafferty
5
Stefan Zielonka
4
Rene Hoet
6*- 1 Other, Cambridge, United Kingdom
- 2 Discovery & Engineering Division, Iontas Ltd./FairJourney Biologics, Cambridge, United Kingdom
- 3 Technology Division, Iontas Ltd./FairJourney Biologics, Cambridge, United Kingdom
- 4 Antibody Discovery & Protein Engineering, Merck Healthcare KGaA, Darmstadt, Germany
- 5 Maxion Therapeutics, Cambridge, United Kingdom
- 6 Technology Division, FairJourney Biologics, Porto, Portugal & Iontas, Cambridge, United Kingdom, Porto, Portugal
The evolving development landscape of biotherapeutics and their growing complexity from simple antibodies into bi-and multi-specific molecules necessitates sophisticated discovery and engineering platforms. This review focuses on mammalian display technology as a potential solution to the pressing challenges in biotherapeutic development. We provide a comparative analysis with established methodologies, highlighting key aspects of mammalian display technology, including genetic engineering, construction of display libraries, and its pivotal role in hit selection and/or developability engineering. The review delves into the mechanisms underpinning developability-driven selection via mammalian display and their broader implications. Applications beyond antibody discovery are also explored, alongside advancements towards function-first screening technologies, precision genome engineering and AI/ML-enhanced libraries, situating them in the context of mammalian display. Overall, the review provides a comprehensive overview of the current mammalian display technology landscape, underscores the expansive potential of the technology for biotherapeutic development, addresses the critical challenges for the full realisation of this potential, and examines advances in related disciplines that might impact the future application of mammalian display technologies.
Keywords: Antibody engineering, Antibody libraries, biologics discovery technologies, developability screening, functional screening, Genetic Engineering
Received: 23 Jul 2024; Accepted: 04 Sep 2024.
Copyright: © 2024 Slavny, Hegde, Doerner, Parthiban, McCafferty, Zielonka and Hoet. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Peter Slavny, Other, Cambridge, United Kingdom
Manjunath Hegde, Technology Division, Iontas Ltd./FairJourney Biologics, Cambridge, United Kingdom
Rene Hoet, Technology Division, FairJourney Biologics, Porto, Portugal & Iontas, Cambridge, United Kingdom, Porto, Portugal
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