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

• Main Authors: Manisha Ray, Yasuyuki Kihara, Darryl J. Bornhop, Jerold Chun
• Format: Article
• Language: English
• Published: BMC 2021-04-01
• Series: Lipids in Health and Disease
• Subjects: Lysophosphatidic acid; Compensated interferometric reader; Ligand binding; Antibody; Lpathomab; Lysophospholipid
• Online Access: https://doi.org/10.1186/s12944-021-01454-4

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.