CX3CR1 has been identified as a highly attractive target for several therapeutic interventions. Despite this potential, no potent antagonists, either small molecule or monoclonal antibody, have been identified. Here we describe the lead finding and engineering approach that lead to the identification of BI 655088, a potent biotherapeutic antagonist to CX3CR1. BI 655088 is a potent CX3CR1 antagonist that, upon therapeutic dosing, significantly inhibits plaque progression in the standard mouse model of atherosclerosis. BI 655088 represents a novel and highly selective biotherapeutic that could reduce inflammation in the atherosclerotic plaque when added to standard of care treatment including statins, which could result in a significant decrease in atherothrombotic events in patients with existing cardiovascular disease.

中文翻译：

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靶向趋化因子受体 CX3CR1 的 VHH 抗体可抑制动脉粥样硬化的进展。

CX3CR1 已被确定为几种治疗干预的极具吸引力的靶标。尽管有这种潜力，但尚未鉴定出有效的拮抗剂，无论是小分子还是单克隆抗体。在这里，我们描述了导致识别 BI 655088 的先导发现和工程方法，BI 655088 是一种有效的 CX3CR1 生物治疗拮抗剂。BI 655088 是一种有效的 CX3CR1 拮抗剂，在治疗剂量后，可显着抑制标准动脉粥样硬化小鼠模型中的斑块进展。BI 655088 代表了一种新型且高度选择性的生物治疗药物，当添加到包括他汀类药物在内的标准护理治疗中时，可以减少动脉粥样硬化斑块的炎症，这可能会显着减少现有心血管疾病患者的动脉粥样硬化血栓事件。