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A natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade
Human urinary proteins are a goldmine of natural proteins a feature that simplifies their translation to biologics. Combining this goldmine together with the ligand-affinity-chromatography (LAC) purification method, proved a winning formula in their isolation. LAC specificity, efficiency, simplicity...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980337/ https://www.ncbi.nlm.nih.gov/pubmed/36875111 http://dx.doi.org/10.3389/fimmu.2023.1151620 |
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author | Novick, Daniela |
author_facet | Novick, Daniela |
author_sort | Novick, Daniela |
collection | PubMed |
description | Human urinary proteins are a goldmine of natural proteins a feature that simplifies their translation to biologics. Combining this goldmine together with the ligand-affinity-chromatography (LAC) purification method, proved a winning formula in their isolation. LAC specificity, efficiency, simplicity and inherent indispensability in the search for predictable and unpredictable proteins, is superior to other separation techniques. Unlimited amounts of recombinant cytokines and monoclonal antibodies (mAb) accelerated the “triumph”. My approach concluded 35 years of worldwide pursuit for Type I IFN receptor (IFNAR2) and advanced the understanding of the signal transduction of this Type of IFN. TNF, IFNγ and IL-6 as baits enabled the isolation of their corresponding soluble receptors and N-terminal amino acid sequence of the isolated proteins facilitated the cloning of their cell surface counterparts. IL-18, IL-32, and heparanase as the baits yielded the corresponding unpredictable proteins: the antidote IL-18 Binding Protein (IL-18BP), the enzyme Proteinase 3 (PR3) and the hormone Resistin. IFNβ proved beneficial in Multiple Sclerosis and is a blockbuster drug, Rebif(®). TNF mAbs translated into Remicade(®) to treat Crohn’s disease. Enbrel(®) based on TBPII is for Rheumatoid Arthritis. Both are blockbusters. Tadekinig alfa™, a recombinant IL-18BP, is in phase III clinical study for inflammatory and autoimmune diseases. Seven years of continuous compassionate use of Tadekinig alfa™ in children born with mutations (NLRC4, XIAP) proved life-saving and is an example of tailored made medicine. IL-18 is a checkpoint biomarker in cancer and IL-18BP is planned recently to target cytokine storms resulting from CAR-T treatment and in COVID 19. |
format | Online Article Text |
id | pubmed-9980337 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99803372023-03-03 A natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade Novick, Daniela Front Immunol Immunology Human urinary proteins are a goldmine of natural proteins a feature that simplifies their translation to biologics. Combining this goldmine together with the ligand-affinity-chromatography (LAC) purification method, proved a winning formula in their isolation. LAC specificity, efficiency, simplicity and inherent indispensability in the search for predictable and unpredictable proteins, is superior to other separation techniques. Unlimited amounts of recombinant cytokines and monoclonal antibodies (mAb) accelerated the “triumph”. My approach concluded 35 years of worldwide pursuit for Type I IFN receptor (IFNAR2) and advanced the understanding of the signal transduction of this Type of IFN. TNF, IFNγ and IL-6 as baits enabled the isolation of their corresponding soluble receptors and N-terminal amino acid sequence of the isolated proteins facilitated the cloning of their cell surface counterparts. IL-18, IL-32, and heparanase as the baits yielded the corresponding unpredictable proteins: the antidote IL-18 Binding Protein (IL-18BP), the enzyme Proteinase 3 (PR3) and the hormone Resistin. IFNβ proved beneficial in Multiple Sclerosis and is a blockbuster drug, Rebif(®). TNF mAbs translated into Remicade(®) to treat Crohn’s disease. Enbrel(®) based on TBPII is for Rheumatoid Arthritis. Both are blockbusters. Tadekinig alfa™, a recombinant IL-18BP, is in phase III clinical study for inflammatory and autoimmune diseases. Seven years of continuous compassionate use of Tadekinig alfa™ in children born with mutations (NLRC4, XIAP) proved life-saving and is an example of tailored made medicine. IL-18 is a checkpoint biomarker in cancer and IL-18BP is planned recently to target cytokine storms resulting from CAR-T treatment and in COVID 19. Frontiers Media S.A. 2023-02-16 /pmc/articles/PMC9980337/ /pubmed/36875111 http://dx.doi.org/10.3389/fimmu.2023.1151620 Text en Copyright © 2023 Novick https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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. |
spellingShingle | Immunology Novick, Daniela A natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade |
title | A natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade |
title_full | A natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade |
title_fullStr | A natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade |
title_full_unstemmed | A natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade |
title_short | A natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade |
title_sort | natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980337/ https://www.ncbi.nlm.nih.gov/pubmed/36875111 http://dx.doi.org/10.3389/fimmu.2023.1151620 |
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