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Lysophosphatidic acid (LPA)-antibody (504B3) engagement detected by interferometry identifies off-target binding

BACKGROUND: Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that acts through its six cognate G protein-coupled receptors. As a family, lysophospholipids have already produced medicines (e.g., sphingosine 1-phosphate) as is being pursued for LPA through the use of specific antibodies tha...

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Autores principales: Ray, Manisha, Kihara, Yasuyuki, Bornhop, Darryl J., Chun, Jerold
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048308/
https://www.ncbi.nlm.nih.gov/pubmed/33853612
http://dx.doi.org/10.1186/s12944-021-01454-4
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author Ray, Manisha
Kihara, Yasuyuki
Bornhop, Darryl J.
Chun, Jerold
author_facet Ray, Manisha
Kihara, Yasuyuki
Bornhop, Darryl J.
Chun, Jerold
author_sort Ray, Manisha
collection PubMed
description BACKGROUND: Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that acts through its six cognate G protein-coupled receptors. As a family, lysophospholipids have already produced medicines (e.g., sphingosine 1-phosphate) as is being pursued for LPA through the use of specific antibodies that reduce ligand availability. METHODS: The binding properties of a commercially available, reportedly specific, monoclonal LPA antibody named 504B3 that is related to the clinical candidate Lpathomab/LT3015 were reexamined using a free solution assay (FSA) measured in a compensated interferometric reader (CIR). RESULTS: Measurement of 504B3 binding properties with an FSA-CIR approach revealed similar binding affinities for 504B3 against LPA as well as the non-LPA lipids, phosphatidic acid (PA) and lysophosphatidylcholine (LPC). CONCLUSIONS: Antibody binding specificity and sensitivity, particularly involving lipid ligands, can be assessed in solution and without labels using FSA-CIR. These findings could affect interpretations of both current and past basic and clinical studies employing 504B3 and related anti-LPA antibodies.
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spelling pubmed-80483082021-04-15 Lysophosphatidic acid (LPA)-antibody (504B3) engagement detected by interferometry identifies off-target binding Ray, Manisha Kihara, Yasuyuki Bornhop, Darryl J. Chun, Jerold Lipids Health Dis Short Report BACKGROUND: Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that acts through its six cognate G protein-coupled receptors. As a family, lysophospholipids have already produced medicines (e.g., sphingosine 1-phosphate) as is being pursued for LPA through the use of specific antibodies that reduce ligand availability. METHODS: The binding properties of a commercially available, reportedly specific, monoclonal LPA antibody named 504B3 that is related to the clinical candidate Lpathomab/LT3015 were reexamined using a free solution assay (FSA) measured in a compensated interferometric reader (CIR). RESULTS: Measurement of 504B3 binding properties with an FSA-CIR approach revealed similar binding affinities for 504B3 against LPA as well as the non-LPA lipids, phosphatidic acid (PA) and lysophosphatidylcholine (LPC). CONCLUSIONS: Antibody binding specificity and sensitivity, particularly involving lipid ligands, can be assessed in solution and without labels using FSA-CIR. These findings could affect interpretations of both current and past basic and clinical studies employing 504B3 and related anti-LPA antibodies. BioMed Central 2021-04-14 /pmc/articles/PMC8048308/ /pubmed/33853612 http://dx.doi.org/10.1186/s12944-021-01454-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Short Report
Ray, Manisha
Kihara, Yasuyuki
Bornhop, Darryl J.
Chun, Jerold
Lysophosphatidic acid (LPA)-antibody (504B3) engagement detected by interferometry identifies off-target binding
title Lysophosphatidic acid (LPA)-antibody (504B3) engagement detected by interferometry identifies off-target binding
title_full Lysophosphatidic acid (LPA)-antibody (504B3) engagement detected by interferometry identifies off-target binding
title_fullStr Lysophosphatidic acid (LPA)-antibody (504B3) engagement detected by interferometry identifies off-target binding
title_full_unstemmed Lysophosphatidic acid (LPA)-antibody (504B3) engagement detected by interferometry identifies off-target binding
title_short Lysophosphatidic acid (LPA)-antibody (504B3) engagement detected by interferometry identifies off-target binding
title_sort lysophosphatidic acid (lpa)-antibody (504b3) engagement detected by interferometry identifies off-target binding
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048308/
https://www.ncbi.nlm.nih.gov/pubmed/33853612
http://dx.doi.org/10.1186/s12944-021-01454-4
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AT bornhopdarrylj lysophosphatidicacidlpaantibody504b3engagementdetectedbyinterferometryidentifiesofftargetbinding
AT chunjerold lysophosphatidicacidlpaantibody504b3engagementdetectedbyinterferometryidentifiesofftargetbinding