IOS-1002是一种稳定HLA-B57开放格式,具有强大的抗瘤活性
Anahita Rafiei1, Marco Gualandi1, Chia-Lung Yang1
1ImmunOs Therapeutics AG, 8952 Schlieren, Switzerland.
Cancers
|August 29, 2024
概括
一种新的融合蛋白,IOS-1002,针对免疫检查点来激活抗瘤免疫力. 这种人类白细胞抗原 (HLA) 分子在临床前模型中显示出有效性,增强了T和NK细胞对抗癌症的活性.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 结构生物学 结构生物学
背景情况:
- 人类白细胞抗原 (HLA) 类I分子,特别是HLA-B27和HLA-B57,已知在自身免疫和病毒免疫中起作用.
- 它们对癌症免疫的参与,特别是与LILRB和KIR等先天性免疫检查点受体的相互作用,尚不清楚.
研究的目的:
- 研究HLA-B57在癌症免疫中的作用.
- 开发和描述一种新型的融合蛋白,IOS-1002,针对免疫检查点进行抗瘤活性.
主要方法:
- 设计了一个开放格式的,稳定性优化的HLA-B57-B2m-IgG4_Fc融合蛋白 (IOS-1002).
- 评估IOS-1002与LILRB1,LILRB2和KIR3DL1.1的结合情况.
- 评估了Fcγ受体的参与,巨细胞化以及对免疫抑制信号通路和细胞分化的影响.
- 在患者衍生的 ex vivo 瘤模型中测试了 IOS-1002 的疗效.
主要成果:
- IOS-1002与LILRB1,LILRB2和KIR3DL1.1结合在一起
- IgG4 Fc骨干调解Fcγ受体的参与,并增强巨细胞的细胞化.
- IOS-1002抑制免疫抑制信号,减少M2巨细胞的两极分化和骨髓系衍生抑制细胞的分化.
- IOS-1002增强了瘤细胞的细胞化,增强了T和NK细胞的激活,并在瘤模型中显示出有效性.
结论:
- IOS-1002是第一类,多目标和多功能HLA融合蛋白.
- 它通过调节免疫检查点和细胞反应,有效地激活抗瘤免疫力.
- IOS-1002对癌症免疫治疗具有前景,目前正在临床评估中.
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