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向巨细胞的组合疗法增强了T-DXd诱导的瘤回归

Bingyu Li¹, Shanlong Wang², Xiaohui Li³

¹College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, Henan, China; School of Life Sciences and Technology, Tongji University, Shanghai, China.

International immunopharmacology

|March 15, 2025

概括

将trastuzumab deruxtecan (T-DXd) 与针对巨细胞的疗法 (如抗SIRPα抗体和PI3Kγ抑制剂) 结合起来,对HER2阳性癌症有很大的前景. 这种三重疗法增强了抗瘤免疫力,克服了抵抗力,导致瘤回归和持久的记忆力.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
药理学药理学是指药理学的学科.

背景情况:

抗体药物联结物 (ADCs),如特拉斯图祖马布德鲁克斯坦 (T-DXd),对抗HER2阳性癌症是有效的.
治疗耐药性限制了ADC单一治疗的疗效.
瘤相关巨细胞 (TAMs) 在瘤微环境和免疫规避中发挥着关键作用.

研究的目的:

调查结合T-DXd与巨细胞向剂 (抗SIRPα抗体和PI3Kγ抑制剂) 的协同作用潜力.
评估这种三重组合对抗瘤免疫力和克服抵抗力的影响,在HER2阳性癌症模型中.
通过组合疗法评估免疫细胞死亡 (ICD) 诱导和TAM重编程.

主要方法:

使用了HER2阳性临床前癌症模型.
服用组合疗法,包括T-DXd,抗SIRPα抗体和PI3Kγ抑制剂 (IPI-549).
评估瘤生长抑制,耐受性 (体重),免疫细胞死亡,TAM重编程和瘤挑战后的免疫记忆.

主要成果:

与单一疗法相比,三重组合显著抑制了瘤生长,耐受性良好.
连续使用组合疗法导致增强瘤控制,在某些情况下完全回归.
用这种组合治疗的小鼠开发了持久的免疫记忆,拒绝了随后的瘤挑战.

结论:

将T-DXd与向巨细胞的疗法 (抗SIRPα和PI3Kγ抑制剂) 结合起来,对于HER2阳性癌症是一种有前途的策略.
这种方法增强了抗瘤免疫力,克服了抵抗力,并诱导了持久的免疫记忆.
这些发现支持这种组合疗法的进一步临床开发,以改善癌症治疗结果.

关键词:

抗体与药物联合体 (ADCs) 是一种抗体与药物联合体.组合免疫疗法是一种联合免疫疗法.向巨细胞的治疗方法通过SIRPα/PI3Kγ进行SIRPα/PI3Kγ封锁.特拉斯图祖马布德鲁克斯泰干 (T-DXd) 的使用

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