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Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies
Heavy chain-only antibodies (HCAbs) do not associate with light chains and their V(H) regions are functional as single domains, forming the smallest active antibody fragment. These V(H) regions are ideal building blocks for a variety of antibody-based biologics because they tolerate fusion to other...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330309/ https://www.ncbi.nlm.nih.gov/pubmed/30666250 http://dx.doi.org/10.3389/fimmu.2018.03037 |
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author | Clarke, Starlynn C. Ma, Biao Trinklein, Nathan D. Schellenberger, Ute Osborn, Michael J. Ouisse, Laure-Hélène Boudreau, Andrew Davison, Laura M. Harris, Katherine E. Ugamraj, Harshad S. Balasubramani, Aarti Dang, Kevin H. Jorgensen, Brett Ogana, Heather Anne N. Pham, Duy T. Pratap, Payal P. Sankaran, Preethi Anegon, Ignacio van Schooten, Wim C. Brüggemann, Marianne Buelow, Roland Force Aldred, Shelley |
author_facet | Clarke, Starlynn C. Ma, Biao Trinklein, Nathan D. Schellenberger, Ute Osborn, Michael J. Ouisse, Laure-Hélène Boudreau, Andrew Davison, Laura M. Harris, Katherine E. Ugamraj, Harshad S. Balasubramani, Aarti Dang, Kevin H. Jorgensen, Brett Ogana, Heather Anne N. Pham, Duy T. Pratap, Payal P. Sankaran, Preethi Anegon, Ignacio van Schooten, Wim C. Brüggemann, Marianne Buelow, Roland Force Aldred, Shelley |
author_sort | Clarke, Starlynn C. |
collection | PubMed |
description | Heavy chain-only antibodies (HCAbs) do not associate with light chains and their V(H) regions are functional as single domains, forming the smallest active antibody fragment. These V(H) regions are ideal building blocks for a variety of antibody-based biologics because they tolerate fusion to other molecules and may also be attached in series to construct multispecific antibodies without the need for protein engineering to ensure proper heavy and light chain pairing. Production of human HCAbs has been impeded by the fact that natural human V(H) regions require light chain association and display poor biophysical characteristics when expressed in the absence of light chains. Here, we present an innovative platform for the rapid development of diverse sets of human HCAbs that have been selected in vivo. Our unique approach combines antibody repertoire analysis with immunization of transgenic rats, called UniRats, that produce chimeric HCAbs with fully human V(H) domains in response to an antigen challenge. UniRats express HCAbs from large transgenic loci representing the entire productive human heavy chain V(D)J repertoire, mount robust immune responses to a wide array of antigens, exhibit diverse V gene usage and generate large panels of stable, high affinity, antigen-specific molecules. |
format | Online Article Text |
id | pubmed-6330309 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63303092019-01-21 Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies Clarke, Starlynn C. Ma, Biao Trinklein, Nathan D. Schellenberger, Ute Osborn, Michael J. Ouisse, Laure-Hélène Boudreau, Andrew Davison, Laura M. Harris, Katherine E. Ugamraj, Harshad S. Balasubramani, Aarti Dang, Kevin H. Jorgensen, Brett Ogana, Heather Anne N. Pham, Duy T. Pratap, Payal P. Sankaran, Preethi Anegon, Ignacio van Schooten, Wim C. Brüggemann, Marianne Buelow, Roland Force Aldred, Shelley Front Immunol Immunology Heavy chain-only antibodies (HCAbs) do not associate with light chains and their V(H) regions are functional as single domains, forming the smallest active antibody fragment. These V(H) regions are ideal building blocks for a variety of antibody-based biologics because they tolerate fusion to other molecules and may also be attached in series to construct multispecific antibodies without the need for protein engineering to ensure proper heavy and light chain pairing. Production of human HCAbs has been impeded by the fact that natural human V(H) regions require light chain association and display poor biophysical characteristics when expressed in the absence of light chains. Here, we present an innovative platform for the rapid development of diverse sets of human HCAbs that have been selected in vivo. Our unique approach combines antibody repertoire analysis with immunization of transgenic rats, called UniRats, that produce chimeric HCAbs with fully human V(H) domains in response to an antigen challenge. UniRats express HCAbs from large transgenic loci representing the entire productive human heavy chain V(D)J repertoire, mount robust immune responses to a wide array of antigens, exhibit diverse V gene usage and generate large panels of stable, high affinity, antigen-specific molecules. Frontiers Media S.A. 2019-01-07 /pmc/articles/PMC6330309/ /pubmed/30666250 http://dx.doi.org/10.3389/fimmu.2018.03037 Text en Copyright © 2019 Clarke, Ma, Trinklein, Schellenberger, Osborn, Ouisse, Boudreau, Davison, Harris, Ugamraj, Balasubramani, Dang, Jorgensen, Ogana, Pham, Pratap, Sankaran, Anegon, van Schooten, Brüggemann, Buelow and Force Aldred. http://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 Clarke, Starlynn C. Ma, Biao Trinklein, Nathan D. Schellenberger, Ute Osborn, Michael J. Ouisse, Laure-Hélène Boudreau, Andrew Davison, Laura M. Harris, Katherine E. Ugamraj, Harshad S. Balasubramani, Aarti Dang, Kevin H. Jorgensen, Brett Ogana, Heather Anne N. Pham, Duy T. Pratap, Payal P. Sankaran, Preethi Anegon, Ignacio van Schooten, Wim C. Brüggemann, Marianne Buelow, Roland Force Aldred, Shelley Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies |
title | Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies |
title_full | Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies |
title_fullStr | Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies |
title_full_unstemmed | Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies |
title_short | Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies |
title_sort | multispecific antibody development platform based on human heavy chain antibodies |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330309/ https://www.ncbi.nlm.nih.gov/pubmed/30666250 http://dx.doi.org/10.3389/fimmu.2018.03037 |
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