建立新的抗TIM-3抗体,干扰其与配体的结合
Zhuohong Yan1, Teng Ma1, Xiaojue Wang1
1Cancer Research Center, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China.
Heliyon
|April 1, 2024
概括
开发了针对T细胞免疫球蛋白和含有-3 (TIM-3) 的粘真菌域的新单克隆抗体. 这些抗体,特别是那些针对构造性表位体的抗体,显示出阻断TIM-3连接体相互作用的潜力,并在癌症免疫疗法中增强抗瘤免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症研究 癌症研究
- 药物发现 药物发现 药物发现
背景情况:
- 含有T细胞免疫球蛋白和粘素域-3 (TIM-3) 是调节T细胞功能的关键受体,也是癌症免疫疗法的有前途标.
- 蒂姆-3的抑制作用通过与其连接体的相互作用进行介导,但其精确的机制尚未完全理解.
- 阻断TIM-3-连接物相互作用有可能重新激活T细胞并增强抗瘤免疫力.
研究的目的:
- 开发和描述针对人类TIM-3的新型单克隆抗体 (mAbs).
- 为了研究这些mAbs的表皮质结合特征和交叉反应性.
- 评估这些mAbs抑制TIM-3连接体相互作用的能力及其对癌症免疫疗法的影响.
主要方法:
- 开发一个由四个反人类TIM-3 mAbs (MsT001, MsT065, MsT229, MsT286) 组成的小组.
- mAb灵敏度,亲和力和表位识别的表征 (线性与符合性).
- 评估mAb与 cynomolgus TIM-3的交叉反应性以及TIM-3/联结体相互作用的抑制 (Gal-9,HMGB-1,CEACAM-1).
主要成果:
- 开发的mAbs对TIM-3具有很高的敏感性和亲和力.
- 观察到明显的表皮质结合:MsT001/MsT065的线性和MsT229/MsT286.6的合规性.
- MsT229和MsT286抑制了TIM-3与Gal-9,HMGB-1和CEACAM-1的相互作用,并对TIM-3/Gal-9结合的剂量依赖抑制.
结论:
- 在TIM-3上的符合性表位对其连接体相互作用至关重要.
- 成功生成了针对构造性表位体的新型反TIM-3 mAbs.
- 这些mAbs显示出抑制潜力,为向癌症免疫治疗中的TIM-3提供了新的策略.
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