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Complementary epitopes and favorable developability of monoclonal anti-LAMP1 antibodies generated using two transgenic animal platforms

Monoclonal antibodies (mAbs) for therapeutic applications should be as similar to native human antibodies as possible to minimize their immunogenicity in patients. Several transgenic animal platforms are available for the generation of fully human mAbs. Attributes such as specificity, efficacy and C...

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Autores principales: Cameron, Beatrice, Dabdoubi, Tarik, Berthou-Soulié, Laurence, Gagnaire, Marie, Arnould, Isabelle, Severac, Anne, Soubrier, Fabienne, Morales, Jacqueline, Leighton, Philip A., Harriman, William, Ching, Kathryn, Abdiche, Yasmina, Radošević, Katarina, Bouquin, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365404/
https://www.ncbi.nlm.nih.gov/pubmed/32673351
http://dx.doi.org/10.1371/journal.pone.0235815
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author Cameron, Beatrice
Dabdoubi, Tarik
Berthou-Soulié, Laurence
Gagnaire, Marie
Arnould, Isabelle
Severac, Anne
Soubrier, Fabienne
Morales, Jacqueline
Leighton, Philip A.
Harriman, William
Ching, Kathryn
Abdiche, Yasmina
Radošević, Katarina
Bouquin, Thomas
author_facet Cameron, Beatrice
Dabdoubi, Tarik
Berthou-Soulié, Laurence
Gagnaire, Marie
Arnould, Isabelle
Severac, Anne
Soubrier, Fabienne
Morales, Jacqueline
Leighton, Philip A.
Harriman, William
Ching, Kathryn
Abdiche, Yasmina
Radošević, Katarina
Bouquin, Thomas
author_sort Cameron, Beatrice
collection PubMed
description Monoclonal antibodies (mAbs) for therapeutic applications should be as similar to native human antibodies as possible to minimize their immunogenicity in patients. Several transgenic animal platforms are available for the generation of fully human mAbs. Attributes such as specificity, efficacy and Chemistry, Manufacturing and Controls (CMC) developability of antibodies against a specific target are typically established for antibodies obtained from one platform only. In this study, monoclonal antibodies (mAbs) cross-reactive against human and cynomolgus LAMP1 were derived from the human immunoglobulin transgenic TRIANNI mouse and OmniChicken(®) platforms and assessed for their specificity, sequence diversity, ability to bind to and internalize into tumor cells, expected immunogenicity and CMC developability. Our results show that the two platforms were complementary at providing a large diversity of mAbs with respect to epitope coverage and antibody sequence diversity. Furthermore, most antibodies originating from either platform exhibited good manufacturability characteristics.
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spelling pubmed-73654042020-07-27 Complementary epitopes and favorable developability of monoclonal anti-LAMP1 antibodies generated using two transgenic animal platforms Cameron, Beatrice Dabdoubi, Tarik Berthou-Soulié, Laurence Gagnaire, Marie Arnould, Isabelle Severac, Anne Soubrier, Fabienne Morales, Jacqueline Leighton, Philip A. Harriman, William Ching, Kathryn Abdiche, Yasmina Radošević, Katarina Bouquin, Thomas PLoS One Research Article Monoclonal antibodies (mAbs) for therapeutic applications should be as similar to native human antibodies as possible to minimize their immunogenicity in patients. Several transgenic animal platforms are available for the generation of fully human mAbs. Attributes such as specificity, efficacy and Chemistry, Manufacturing and Controls (CMC) developability of antibodies against a specific target are typically established for antibodies obtained from one platform only. In this study, monoclonal antibodies (mAbs) cross-reactive against human and cynomolgus LAMP1 were derived from the human immunoglobulin transgenic TRIANNI mouse and OmniChicken(®) platforms and assessed for their specificity, sequence diversity, ability to bind to and internalize into tumor cells, expected immunogenicity and CMC developability. Our results show that the two platforms were complementary at providing a large diversity of mAbs with respect to epitope coverage and antibody sequence diversity. Furthermore, most antibodies originating from either platform exhibited good manufacturability characteristics. Public Library of Science 2020-07-16 /pmc/articles/PMC7365404/ /pubmed/32673351 http://dx.doi.org/10.1371/journal.pone.0235815 Text en © 2020 Cameron et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Cameron, Beatrice
Dabdoubi, Tarik
Berthou-Soulié, Laurence
Gagnaire, Marie
Arnould, Isabelle
Severac, Anne
Soubrier, Fabienne
Morales, Jacqueline
Leighton, Philip A.
Harriman, William
Ching, Kathryn
Abdiche, Yasmina
Radošević, Katarina
Bouquin, Thomas
Complementary epitopes and favorable developability of monoclonal anti-LAMP1 antibodies generated using two transgenic animal platforms
title Complementary epitopes and favorable developability of monoclonal anti-LAMP1 antibodies generated using two transgenic animal platforms
title_full Complementary epitopes and favorable developability of monoclonal anti-LAMP1 antibodies generated using two transgenic animal platforms
title_fullStr Complementary epitopes and favorable developability of monoclonal anti-LAMP1 antibodies generated using two transgenic animal platforms
title_full_unstemmed Complementary epitopes and favorable developability of monoclonal anti-LAMP1 antibodies generated using two transgenic animal platforms
title_short Complementary epitopes and favorable developability of monoclonal anti-LAMP1 antibodies generated using two transgenic animal platforms
title_sort complementary epitopes and favorable developability of monoclonal anti-lamp1 antibodies generated using two transgenic animal platforms
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365404/
https://www.ncbi.nlm.nih.gov/pubmed/32673351
http://dx.doi.org/10.1371/journal.pone.0235815
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