Recent Advances in the Molecular Design and Applications of Multispecific Biotherapeutics

Recombinant protein-based biotherapeutics drugs have transformed clinical pipelines of the biopharmaceutical industry since the launch of recombinant insulin nearly four decades ago. These biologic drugs are structurally more complex than small molecules, and yet share a similar principle for ration...

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Main Authors: Xiaotian Zhong, Aaron M. D’Antona
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Antibodies
Subjects:
Online Access:https://www.mdpi.com/2073-4468/10/2/13
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author Xiaotian Zhong
Aaron M. D’Antona
author_facet Xiaotian Zhong
Aaron M. D’Antona
author_sort Xiaotian Zhong
collection DOAJ
description Recombinant protein-based biotherapeutics drugs have transformed clinical pipelines of the biopharmaceutical industry since the launch of recombinant insulin nearly four decades ago. These biologic drugs are structurally more complex than small molecules, and yet share a similar principle for rational drug discovery and development: That is to start with a pre-defined target and follow with the functional modulation with a therapeutic agent. Despite these tremendous successes, this “one target one drug” paradigm has been challenged by complex disease mechanisms that involve multiple pathways and demand new therapeutic routes. A rapidly evolving wave of multispecific biotherapeutics is coming into focus. These new therapeutic drugs are able to engage two or more protein targets via distinct binding interfaces with or without the chemical conjugation to large or small molecules. They possess the potential to not only address disease intricacy but also exploit new therapeutic mechanisms and assess undruggable targets for conventional monospecific biologics. This review focuses on the recent advances in molecular design and applications of major classes of multispecific biotherapeutics drugs, which include immune cells engagers, antibody-drug conjugates, multispecific tetherbodies, biologic matchmakers, and small-scaffold multispecific modalities. Challenges posed by the multispecific biotherapeutics drugs and their future outlooks are also discussed.
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spelling doaj.art-5df28ad846a8472eb68b13ef6c7265c22023-11-21T13:22:43ZengMDPI AGAntibodies2073-44682021-03-011021310.3390/antib10020013Recent Advances in the Molecular Design and Applications of Multispecific BiotherapeuticsXiaotian Zhong0Aaron M. D’Antona1Department of BioMedicine Design, Medicinal Sciences, Pfizer Worldwide R&D, 610 Main Street, Cambridge, MA 02139, USADepartment of BioMedicine Design, Medicinal Sciences, Pfizer Worldwide R&D, 610 Main Street, Cambridge, MA 02139, USARecombinant protein-based biotherapeutics drugs have transformed clinical pipelines of the biopharmaceutical industry since the launch of recombinant insulin nearly four decades ago. These biologic drugs are structurally more complex than small molecules, and yet share a similar principle for rational drug discovery and development: That is to start with a pre-defined target and follow with the functional modulation with a therapeutic agent. Despite these tremendous successes, this “one target one drug” paradigm has been challenged by complex disease mechanisms that involve multiple pathways and demand new therapeutic routes. A rapidly evolving wave of multispecific biotherapeutics is coming into focus. These new therapeutic drugs are able to engage two or more protein targets via distinct binding interfaces with or without the chemical conjugation to large or small molecules. They possess the potential to not only address disease intricacy but also exploit new therapeutic mechanisms and assess undruggable targets for conventional monospecific biologics. This review focuses on the recent advances in molecular design and applications of major classes of multispecific biotherapeutics drugs, which include immune cells engagers, antibody-drug conjugates, multispecific tetherbodies, biologic matchmakers, and small-scaffold multispecific modalities. Challenges posed by the multispecific biotherapeutics drugs and their future outlooks are also discussed.https://www.mdpi.com/2073-4468/10/2/13multispecific biotherapeuticsimmune cells engagersantibody-drug conjugatesmultispecific tetherbodiesbiologic matchmakerssmall-scaffold multispecific modalities
spellingShingle Xiaotian Zhong
Aaron M. D’Antona
Recent Advances in the Molecular Design and Applications of Multispecific Biotherapeutics
Antibodies
multispecific biotherapeutics
immune cells engagers
antibody-drug conjugates
multispecific tetherbodies
biologic matchmakers
small-scaffold multispecific modalities
title Recent Advances in the Molecular Design and Applications of Multispecific Biotherapeutics
title_full Recent Advances in the Molecular Design and Applications of Multispecific Biotherapeutics
title_fullStr Recent Advances in the Molecular Design and Applications of Multispecific Biotherapeutics
title_full_unstemmed Recent Advances in the Molecular Design and Applications of Multispecific Biotherapeutics
title_short Recent Advances in the Molecular Design and Applications of Multispecific Biotherapeutics
title_sort recent advances in the molecular design and applications of multispecific biotherapeutics
topic multispecific biotherapeutics
immune cells engagers
antibody-drug conjugates
multispecific tetherbodies
biologic matchmakers
small-scaffold multispecific modalities
url https://www.mdpi.com/2073-4468/10/2/13
work_keys_str_mv AT xiaotianzhong recentadvancesinthemoleculardesignandapplicationsofmultispecificbiotherapeutics
AT aaronmdantona recentadvancesinthemoleculardesignandapplicationsofmultispecificbiotherapeutics