Development of therapeutic antibodies for the treatment of diseases

Journal of Biomedical Science, Journal Year: 2020, Volume and Issue: 27(1)

Published: Jan. 2, 2020

Abstract It has been more than three decades since the first monoclonal antibody was approved by United States Food and Drug Administration (US FDA) in 1986, during this time, engineering dramatically evolved. Current drugs have increasingly fewer adverse effects due to their high specificity. As a result, therapeutic antibodies become predominant class of new developed recent years. Over past five years, best-selling pharmaceutical market, 2018, eight top ten bestselling worldwide were biologics. The global market valued at approximately US$115.2 billion 2018 is expected generate revenue $150 end 2019 $300 2025. Thus, for experienced explosive growth as treating various human diseases, including many cancers, autoimmune, metabolic infectious diseases. December 2019, 79 mAbs US FDA, but there still significant potential. This review summarizes latest trends outlines preeminent technologies used development drugs, such humanization antibodies, phage display, mouse, single B cell technology, affinity maturation. Finally, future applications perspectives are also discussed.

Language: Английский

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Antibody–drug conjugates for cancer

The Lancet, Journal Year: 2019, Volume and Issue: 394(10200), P. 793 - 804

Published: Aug. 1, 2019

Language: Английский

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Antibody Structure and Function: The Basis for Engineering Therapeutics

Antibodies, Journal Year: 2019, Volume and Issue: 8(4), P. 55 - 55

Published: Dec. 3, 2019

Antibodies and antibody-derived macromolecules have established themselves as the mainstay in protein-based therapeutic molecules (biologics). Our knowledge of structure–function relationships antibodies provides a platform for protein engineering that has been exploited to generate wide range biologics host indications. In this review, our basic understanding antibody structure is described along with how leveraged antibody-related therapeutics having appropriate antigen affinity, effector function, biophysical properties. The platforms examined include development antibodies, fragments, bispecific antibody, fusion products, whose efficacy manufacturability can be improved via humanization, affinity modulation, stability enhancement. We also review design selection binding arms, avidity modulation. Different strategies preparing multispecific an array applications are included.

Language: Английский

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Antibodies to watch in 2020

mAbs, Journal Year: 2019, Volume and Issue: 12(1)

Published: Dec. 18, 2019

This 2020 installment of the annual 'Antibodies to Watch' series documents antibody therapeutics approved in 2019 and regulatory review United States or European Union, as well those late-stage clinical studies, November 2019*. At this time, a total 5 novel (romosozumab, risankizumab, polatuzumab vedotin, brolucizumab, crizanlizumab) had been granted first approval either US EU, marketing applications for 13 (eptinezumab, teprotumumab, enfortumab isatuximab, [fam-]trastuzumab deruxtecan, inebilizumab, leronlimab, sacituzumab govitecan, satralizumab, narsoplimab, tafasitamab, REGNEB3 naxituximab) were undergoing these regions, which represent major markets therapeutics. Also 2019, 79 antibodies evaluation studies. Of antibodies, 39 studies non-cancer indications, with 2 (ublituximab, pamrevlumab) also cancer indications. Companies developing 7 (tanezumab, aducanumab, evinacumab, etrolizumab, sutimlimab, anifrolumab, teplizumab) drugs have indicated that they may submit application EU 2020. 40 treatments cancer, potentially 9 (belantamab mafodotin, oportuzumab monatox, margetuximab, dostarlimab, spartalizumab, 131I-omburtamab, loncastuximab tesirine, balstilimab, zalifrelimab) enter late Overall, biopharmaceutical industry's pipeline is robust, should provide continuous supply innovative products patients future. *Note on key updates through December 18, 2019: 1) Food Drug Administration accelerated vedotin-ejfv (Padcev) bringing number during 6; 2) Commission romosozumab 9, 2019; 3) Medicines Agency issued positive opinion brolucizumab; 4) Sesen Bio initiated rolling biologics license (BLA) 6, 5) GlaxoSmithKline submitted BLA belantamab mafodotin; 6) status Phase 3 study (NCT04128696) GSK3359609, humanized IgG4 anti-ICOS antibody, head neck squamous cell carcinoma was updated recruiting from not yet recruiting.

Language: Английский

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ImmunoPET: Concept, Design, and Applications

Chemical Reviews, Journal Year: 2020, Volume and Issue: 120(8), P. 3787 - 3851

Published: March 23, 2020

Immuno-positron emission tomography (immunoPET) is a paradigm-shifting molecular imaging modality combining the superior targeting specificity of monoclonal antibody (mAb) and inherent sensitivity PET technique. A variety radionuclides mAbs have been exploited to develop immunoPET probes, which has driven by development optimization radiochemistry conjugation strategies. In addition, tumor-targeting vectors with short circulation time (e.g., Nanobody) or an enhanced binding affinity bispecific antibody) are being used design novel probes. Accordingly, several such as

Language: Английский

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Conceptual Approaches to Modulating Antibody Effector Functions and Circulation Half-Life

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: June 7, 2019

Antibodies and Fc-fusion antibody-like proteins have become successful biologics developed for cancer treatment, passive immunity against infection, addiction, autoimmune diseases. In general these biopharmaceuticals can be used blocking protein:protein interactions, crosslinking host receptors to induce signaling, recruiting effector cells targets, fixing complement. With the vast capability of antibodies affect infectious genetic diseases much effort has been placed on improving tailoring specific functions. While antibody:antigen engagement is critical an efficacious antibody biologic, equally as important are hinge constant domains heavy chain. It that engage or complement protein mediate a myriad functions regulate circulation. Molecular structural studies provided insight into how from across different species, isotypes, subclasses, alleles recognized by cell C1q. The molecular details interactions led manipulation sequences glycosylation enhance reduce circulating half-life. This review will describe concepts being applied optimize crystallizable fragment antibodies, it detail tuned up down biological function confers desired disease outcome.

Language: Английский

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Antibodies to watch in 2021

mAbs, Journal Year: 2021, Volume and Issue: 13(1)

Published: Jan. 1, 2021

In this 12th annual installment of the Antibodies to Watch article series, we discuss key events in antibody therapeutics development that occurred 2020 and forecast might occur 2021. The coronavirus disease 2019 (COVID-19) pandemic posed an array challenges opportunities healthcare system 2020, it will continue do so Remarkably, by late November two anti-SARS-CoV products, bamlanivimab casirivimab imdevimab cocktail, were authorized for emergency use US Food Drug Administration (FDA) repurposed antibodies levilimab itolizumab had been registered as treatments COVID-19 Russia India, respectively. Despite pandemic, 10 granted first approval or EU November, 2 more (tanezumab margetuximab) may be approvals December 2020.* addition, prolgolimab olokizumab cetuximab saratolacan sodium was approved Japan. number 2021 set a record, marketing applications 16 investigational are already undergoing regulatory review either FDA European Medicines Agency. Of these mAbs, 11 possible non-cancer indications 5 potential cancer. Based on information publicly available 44 late-stage clinical studies indications, including 6 COVID-19, at least (leronlimab, tezepelumab, faricimab, ligelizumab, garetosmab, fasinumab) planned cancer indications. 44, application submissions 13 submitted end *Note added proof announced during 1-21, 2020: margetuximab-cmkb ansuvimab-zykl 21, respectively; biologics license ublituximab amivantamab.

Language: Английский

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The pharmacology and therapeutic applications of monoclonal antibodies

Pharmacology Research & Perspectives, Journal Year: 2019, Volume and Issue: 7(6)

Published: Dec. 1, 2019

Abstract Monoclonal antibodies (mAbs) have emerged as a major class of therapeutic agents on the market. To date, approximately 80 mAbs been granted marketing approval. In 2018, 12 new were approved by FDA, representing 20% total number drugs. The majority mAb therapeutics are for oncological and immunological/infectious diseases, but these expanding into other disease areas. Over 100 monoclonal in development, their unique features ensure that will remain part pipeline. Thus, value elucidation pharmacological properties supporting clinical development large molecules unquestioned. However, utilization tools academic laboratories has lagged behind small molecule counterparts. Early targeted soluble cytokines, now also target membrane‐bound receptors increased circulating half‐life, pharmacology is more complex. principles enabled high affinity, potent selective with reduced off‐target effects drug‐drug interactions. This review discuss how same basic can be applied to mAbs, some important differences. several benefits, such fewer adverse effects, interactions, higher specificity, potentially efficacy through therapy. Modifications decrease immunogenicity increase described, examples optimizing pharmacokinetic enabling oral bioavailability. Increased awareness advances may help use exploratory research further understand characterize properties.

Language: Английский

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Considerations for the Design of Antibody-Based Therapeutics

Journal of Pharmaceutical Sciences, Journal Year: 2019, Volume and Issue: 109(1), P. 74 - 103

Published: June 4, 2019

Antibody-based proteins have become an important class of biologic therapeutics, due in large part to the stability, specificity, and adaptability antibody framework. Indeed, antibodies not only inherent ability bind both antigens endogenous immune receptors but also proven extremely amenable protein engineering. Thus, several derivatives monoclonal format, including bispecific antibodies, antibody-drug conjugates, fragments, demonstrated efficacy for treating human disease, particularly fields immunology oncology. Reviewed here are considerations design antibody-based immunological context, therapeutic mechanisms, engineering strategies. First, characteristics introduced, with emphasis on structural domains, functionally receptors, isotypic allotypic differences, modifications such as glycosylation. Then, aspects discussed, identification antigen-specific variable regions, choice expression system, use multispecific formats, based fragmentation, oligomerization, or conjugation other functional moieties. Finally, strategies enhance function through reviewed while highlighting impact fundamental biophysical properties developability.

Language: Английский

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Broadly neutralizing anti-HIV-1 monoclonal antibodies in the clinic

Nature Medicine, Journal Year: 2019, Volume and Issue: 25(4), P. 547 - 553

Published: April 1, 2019

Language: Английский

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