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表观遗传剂加上抗PD-1可以重编程瘤微环境,并恢复霍奇金淋巴瘤的抗瘤疗效

Jing Nie¹, Chunmeng Wang¹, Liangtao Zheng²

¹Department of Biotherapeutics, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China.

|August 2, 2024

概括

一种新的三重疗法结合了奇达米德,德西他和卡姆雷利祖马布 (CDP),在以前用DP治疗过的复发性/耐药性经典霍奇金淋巴瘤 (cHL) 患者中显示出高疗效. 这种双重的副免疫疗法克服了耐药性,改善了cHL的结果.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

德西塔加抗PD-1 (DP) 治疗对复发性/耐药性经典霍奇金淋巴瘤 (cHL) 有效.
一部分患者在DP治疗后表现出原发性耐药性或复发,需要使用替代治疗策略.
了解瘤微环境对于克服cHL免疫疗法耐药性至关重要.

研究的目的:

评估三重疗法 (chidamide,decitabine,anti-PD-1 camrelizumab - CDP) 在之前接受DP治疗的cHL患者的疗效和安全性.
调查CDP治疗反应和cHL中耐药性的机制.
探索瘤微环境在调解对双重表皮免疫疗法的反应中的作用.

主要方法:

一个阶段[指定已知的阶段]临床试验,涉及52名患有复发性/耐药性cHL的患者,他们之前接受过DP治疗.
用奇达米德,德西塔宾和卡梅利祖马布 (CDP) 治疗.
瘤活检样本的单细胞RNA测序 (预处理和治疗期间) 用于分析细胞组成和信号通路.

主要成果:

CDP治疗显示高客观反应率 (94%) 和完全反应率 (50%).
所有对先前DP治疗有耐药性的患者都对CDP有反应,与DP敏感患者相比,CR率较低.
无进展生存时间的中位数为29.4个月.
CDP治疗通过激活CD8+T细胞和通过STAT1/3抑制抑制免疫抑制IL21+CD4+T辅助细胞来调节瘤微环境.

结论:

三重CDP疗法在以前暴露于DP的cHL患者中耐受良好,并且非常有效,包括那些具有耐药性的患者.
通过改变瘤的免疫微环境,CDP克服了免疫疗法耐药性.
双重副免疫疗法为治疗复发性/耐药性cHL提供了一个有希望的策略.

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