Advancements in mammalian display technology for therapeutic antibody development and beyond: current landscape, challenges, and future prospects.

antibody engineering antibody libraries biologics discovery technologies developability screening functional screening genetic engineering

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2024
Historique:
received: 23 07 2024
accepted: 04 09 2024
medline: 9 10 2024
pubmed: 9 10 2024
entrez: 9 10 2024
Statut: epublish

Résumé

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.

Identifiants

pubmed: 39381002
doi: 10.3389/fimmu.2024.1469329
pmc: PMC11459229
doi:

Substances chimiques

Antibodies, Monoclonal 0

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

1469329

Informations de copyright

Copyright © 2024 Slavny, Hegde, Doerner, Parthiban, McCafferty, Zielonka and Hoet.

Déclaration de conflit d'intérêts

PS, MH, KP, and RH are affiliated with Iontas/FairJourney Biologics. AD and SZ are affiliated with Merck Healthcare KGaA and may hold its shares. JM is the co-founder of Iontas and inventor of the Iontas Proprietary mammalian display technology and is currently affiliated with Maxion® Therapeutics. Iontas/FairJourney Biologics holds intellectual property in mammalian display technology and offers antibody discovery and engineering services.

Auteurs

Peter Slavny (P)

Discovery & Engineering Division, Iontas Ltd./FairJourney Biologics, Cambridge, United Kingdom.

Manjunath Hegde (M)

Technology Division, Iontas/FairJourney Biologics, Cambridge, United Kingdom.

Achim Doerner (A)

Antibody Discovery & Protein Engineering, Merck Healthcare KGaA, Darmstadt, Germany.

Kothai Parthiban (K)

Discovery & Engineering Division, Iontas Ltd./FairJourney Biologics, Cambridge, United Kingdom.

John McCafferty (J)

Maxion Therapeutics, Cambridge, United Kingdom.
Department of Medicine, University of Cambridge, Cambridge, United Kingdom.

Stefan Zielonka (S)

Antibody Discovery & Protein Engineering, Merck Healthcare KGaA, Darmstadt, Germany.

Rene Hoet (R)

Technology Division, Iontas/FairJourney Biologics, Cambridge, United Kingdom.
Technology Division, FairJourney Biologics, Porto, Portugal.

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Classifications MeSH