通过干涉测量法检测到的溶血磷脂酸（LPA）抗体（504B3）结合可识别非靶标结合。
Lysophosphatidic acid (LPA)-antibody (504B3) engagement detected by interferometry identifies off-target binding.
机构信息
Translational Neuroscience Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
Department of Chemistry and Vanderbilt Institute for Chemical Biology, Nashville, TN, 37235, USA.
出版信息
Lipids Health Dis. 2021 Apr 14;20(1):32. doi: 10.1186/s12944-021-01454-4.
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.
背景
溶血磷脂酸（LPA）是一种具有生物活性的溶血磷脂，通过其六个同源 G 蛋白偶联受体发挥作用。作为一个家族，溶血磷脂已经产生了药物（例如，1-磷酸鞘氨醇），并且正在通过使用减少配体可用性的特异性抗体来追求 LPA。
方法
使用补偿干涉仪读数器（CIR）测量的游离溶液测定法（FSA）重新检查了一种商业上可获得的、据称是特异性的单克隆 LPA 抗体 504B3 的结合特性，该抗体与临床候选药物 Lpathomab/LT3015 有关。
结果
使用 FSA-CIR 方法测量 504B3 的结合特性表明，504B3 对 LPA 以及非 LPA 脂质，如磷脂酸（PA）和溶血磷脂酰胆碱（LPC）的结合亲和力相似。
结论
抗体结合的特异性和敏感性，特别是涉及脂质配体，可以在溶液中使用 FSA-CIR 进行无标记评估。这些发现可能会影响当前和过去使用 504B3 和相关抗 LPA 抗体的基础和临床研究的解释。
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