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

Autor: Manisha Ray, Yasuyuki Kihara, Darryl J. Bornhop, Jerold Chun
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Lipids in Health and Disease, Vol 20, Iss 1, Pp 1-6 (2021)
Druh dokumentu: article
ISSN: 1476-511X
DOI: 10.1186/s12944-021-01454-4
Popis: Abstract 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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