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优化Fc的CD276抗体增强了NK细胞对抗非小细胞肺癌的激活

Sylwia A Stefańczyk^1,2, Xenija Kaiser^1,2, Ilona Hagelstein^1,2

¹Clinical Collaboration Unit Translational Immunology, Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.

Frontiers in immunology

|August 18, 2025

概括

一种新的CD276 (B7-H3) 抗体,8H8_SDIE,增强了天然杀手 (NK) 细胞对抗非小细胞肺癌 (NSCLC) 的活性. 这种方法为对PD-1/PD-L1抑制剂耐药的患者提供了一种新的免疫疗法选择.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物技术是生物技术.

背景情况:

非小细胞肺癌 (NSCLC) 仍然是全球癌症死亡的主要原因.
针对PD-1/PD-L1的免疫检查点抑制剂 (ICI) 改善了NSCLC治疗,但并不普遍有效.
CD276 (B7-H3) 是一个有前途的免疫治疗点,因为它在瘤中的过度表达和免疫逃避中的作用.

研究的目的:

开发和评估一个Fc优化的CD276抗体,8H8_SDIE,用于增强自然杀手 (NK) 细胞介导免疫治疗NSCLC.
研究8H8_SDIE在激活NK细胞对抗CD276阳性NSCLC细胞中的有效性.

主要方法:

开发一种Fc优化的CD276抗体 (8H8_SDIE),具有增强的结合CD16.
在NSCLC细胞系上对CD276的8H8_SDIE结合特异性的临床前评估.
在接受8H8_SDIE治疗时,评估NK细胞激活标记物 (CD69,CD107a) 和细胞毒性媒介释放物 (IFNγ,穿孔素,granzyme B).

主要成果:

8H8_SDIE在NSCLC细胞系上表现出与CD276的特定结合.
用8H8_SDIE治疗显著激活了NK细胞.
激活的NK细胞显示CD69和CD107a的表达增加,并分泌细胞毒性介质.

结论:

在Fc优化的CD276抗体8H8_SDIE有效地参与NK细胞对抗NSCLC.
8H8_SDIE代表了对CD276阳性NSCLC的潜在新型治疗策略,特别是在对PD-1/PD-L1疗法无反应的患者中.
这种基于NK细胞的方法可以克服对传统ICI的耐药性,并为治疗耐火性NSCLC提供新的途径.

关键词:

ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC ADCC is also known as ADCC ADCC ADCC is also known as ADCC CD276 (B7-H3) 是一个在Fc工程方面,工程师在 NK 细胞中, NK 细胞是最重要的.在PD-1/PD-L1非响应者中.免疫疗法免疫疗法这是一种单克隆抗体.非小细胞肺癌 (NSCLC) 是一种非小细胞肺癌.

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