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Identification of monoclonal antibodies suitable for blocking IGF-1 receptors in the horse.
Domestic Animal Endocrinology ( IF 2.1 ) Pub Date : 2020-06-17 , DOI: 10.1016/j.domaniend.2020.106510
S Rahnama 1 , N Vathsangam 2 , R Spence 1 , S T Anderson 3 , M A de Laat 1 , S Bailey 3 , M N Sillence 1
Affiliation  

Prolonged hyperinsulinemia is thought to be the cause of equine endocrinopathic laminitis, a common and crippling disease of the foot, for which there are no pharmacologic treatments other than pain relief. It has been suggested that insulin causes its effects on the lamellae by activating IGF-1 receptors (IGF-1R), as insulin receptors (InsR) are scarce in this tissue, whereas IGF-1R are abundant and become downregulated after prolonged insulin infusion. As a first step toward confirming this mechanism and beginning to develop a therapeutic anti–IGF-1R monoclonal antibody (mAb) for horses, it was necessary to identify available human IGF-1R mAbs that would recognize equine receptors. Four IGF-1R mAbs were tested using soluble equine IGF-1R, with ELISA and flow cytometry. Frozen equine lamellar and liver tissue was also used in radioligand binding assays. The results demonstrated that only one of the mAbs tested (mAb1) was able to compete effectively with IGF-1 for binding to its receptors in equine lamellar tissue, with an IC50 of 5 to 159 ng/mL. None of the 4 mAbs were able to bind to equine hepatic InsR. This study has generated valuable structure-activity information and has identified a prototype anti–IGF-1R mAb suitable for further development.



中文翻译:

鉴定适合阻断马中 IGF-1 受体的单克隆抗体。

长期的高胰岛素血症被认为是马内分泌性蹄叶炎的原因,这是一种常见且致残的足部疾病,除缓解疼痛外没有其他药物治疗方法。有人提出,胰岛素通过激活 IGF-1 受体 (IGF-1R) 对薄片产生影响,因为该组织中胰岛素受体 (InsR) 很少,而 IGF-1R 丰富并在长时间输注胰岛素后下调。作为确认这一机制并开始为马开发治疗性抗 IGF-1R 单克隆抗体 (mAb) 的第一步,有必要确定可识别马受体的可用人 IGF-1R 单克隆抗体。使用可溶性马 IGF-1R、ELISA 和流式细胞术测试了四种 IGF-1R mAb。冷冻马板层和肝脏组织也用于放射性配体结合测定。结果表明,只有一种被测试的 mAb (mAb1) 能够与 IGF-1 有效竞争与马板层组织中其受体的结合,IC50至 159 ng/mL。4 种 mAb 中没有一种能够与马肝 InsR 结合。该研究产生了有价值的结构-活性信息,并确定了一种适合进一步开发的原型抗 IGF-1R mAb。

更新日期:2020-06-17
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