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人体内源性逆转录病毒-H长终端重复关联2:癌症免疫治疗的新兴免疫检查点

Zeya Cao¹, Youping Wang^1,2, Shih-Chin Cheng²

¹Department of Biosciences, Adlai Nortye Biopharma Co., Ltd., No. 1008 Xiangwang Street, Hangzhou 311121, Zhejiang, China.

Journal of leukocyte biology

|July 8, 2024

概括

人体内源性逆转录病毒-H长终端重复关联2 (HHLA2) 是一种新的癌症免疫治疗点. 疗法旨在阻止其抑制信号,同时保持共刺激途径,在早期试验中显示出有前途.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
分子生物学分子生物学

背景情况:

人体内源性逆转录病毒-H长终端重复关联2 (HHLA2) 是B7家族的共同信号分子,在人类癌症中异常表达.
瘤微环境中的HHLA2独特的表达和调节机制有助于其在免疫调节中的复杂作用.
它的矛盾功能导致不同类型癌症的不同预后影响.

研究的目的:

探索HHLA2作为癌症免疫治疗的有希望的目标.
通过其与不同受体的相互作用来阐明HHLA2的双重作用.
评估针对HHLA2免疫检查点的治疗策略.

主要方法:

研究了HHLA2与其受体的相互作用,跨膜和免疫球蛋白含域2 (TMIGD2) 和杀手细胞免疫球蛋白类受体,三个免疫球蛋白域和长细胞质尾巴 (KIR3DL3).
分析了免疫细胞上HHLA2及其受体的表达动态.
在临床前模型中评估了针对HHLA2通路的治疗策略.

主要成果:

HHLA2与TMIGD2相互作用,提供共刺激信号,与KIR3DL3相互作用,传输抑制信号.
HHLA2及其受体的表达模式影响免疫应答平衡.
临床前研究显示了抗HHLA2和抗KIR3DL3抗体的潜力,与PD-1/PD-L1阻断有潜在的协同作用.

结论:

针对HHLA2-KIR3DL3抑制途径,同时保持HHLA2-TMIGD2协同刺激,提供了一种新的免疫治疗方法.
抗HHLA2和抗KIR3DL3抗体正在临床研究中.
针对HHLA2和PD-1/PD-L1的联合疗法可能会由于非重叠的表达模式,增强抗瘤活性.

关键词:

这就是HHLA2的含量.免疫检查点是一个检查点.免疫疗法免疫疗法

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