Clin Cancer Res:JAK1抑制剂Itacitinib可有效预防CAR T细胞疗法引发的细胞因子释放综合征

2020-12-16 Nebula-Qin MedSci原创

细胞因子释放综合征(CRS)是一种严重的、可能危及生命的副作用,通常与CAR-T细胞治疗有关。CRS表现为一种快速免疫反应,由炎症细胞因子过度释放所驱动,包括IFNγ、IFN-3、IFN-6。

嵌合抗原受体(CAR) T细胞是一种很有前途的癌症免疫治疗方法。这种靶向疗法已经在B细胞白血病和淋巴瘤患者中展现出良好的长期无复发生存率。但是,细胞因子释放综合征(CRS)是一种严重的、可能危及生命的副作用,通常与CAR-T细胞治疗有关。CRS表现为一种快速(超快)的免疫反应,由炎症细胞因子过度释放所驱动,包括IFNγ、IFN-3、IFN-6。

已知参与CRS的许多细胞因子都是通过JAK-STAT信号通路发挥作用的。在本研究中,研究人员分析了阻断JAK信号通路对CAR T细胞增殖、抗肿瘤活性和细胞因子水平的影响。

Itacitinib可降低急性炎症小鼠模型的细胞因子水平

Itacitinib可减少巨噬细胞产生的IL6

Itacitinib可减少CAR T细胞的白细胞因子产生

结果显示,itacitinib,一种选择性JAK1抑制剂,可明显以剂量依赖性方式降低参与CRS的多种细胞因子水平,无论是在体内还是体外。

Itacitinib未影响PBMC的增殖或细胞毒性

Itacitinib未减弱T细胞的抗肿瘤活性

重要的是,研究人员还发现,采用临床相关剂量来模拟人JAK1药理抑制时,itacitinib并没有显著抑制三种人CAR T细胞的增殖或抗肿瘤杀伤能力。最后,免疫缺陷的CD19+肿瘤小鼠模型口服itacitinib治疗后,注入到该小鼠体内的CD19-CAR T细胞的抗肿瘤活性减弱。

综上所述,该研究结果表明,itacitinib或可用于预防CAR-T细胞诱导的CRS的发生。一个评估itacitinib用于预防CAR T细胞疗法引发的CRS的II期试验(NCT04071366)已经开展了。

原始出处:

Eduardo Huarte, et al. Itacitinib (INCB039110), a JAK1 Inhibitor, Reduces Cytokines Associated with Cytokine Release Syndrome Induced by CAR T-cell Therapy. Clinical Cancer Research. DOI: 10.1158/1078-0432.CCR-20-1739 Published December 2020

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16 12:11:11 CST 2020, time=2020-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478052, encodeId=46d414e8052ce, content=<a href='/topic/show?id=bb6f18030a4' target=_blank style='color:#2F92EE;'>#T细胞疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18030, encryptionId=bb6f18030a4, topicName=T细胞疗法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6bea7392214, createdName=124984edm24暂无昵称, createdTime=Wed Dec 16 12:11:11 CST 2020, time=2020-12-16, status=1, ipAttribution=)]
    2021-04-16 grace5700
  5. 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16 12:11:11 CST 2020, time=2020-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478052, encodeId=46d414e8052ce, content=<a href='/topic/show?id=bb6f18030a4' target=_blank style='color:#2F92EE;'>#T细胞疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18030, encryptionId=bb6f18030a4, topicName=T细胞疗法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6bea7392214, createdName=124984edm24暂无昵称, createdTime=Wed Dec 16 12:11:11 CST 2020, time=2020-12-16, status=1, ipAttribution=)]
    2021-03-15 yzh399
  6. 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  7. 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16 12:11:11 CST 2020, time=2020-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478052, encodeId=46d414e8052ce, content=<a href='/topic/show?id=bb6f18030a4' target=_blank style='color:#2F92EE;'>#T细胞疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18030, encryptionId=bb6f18030a4, topicName=T细胞疗法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6bea7392214, createdName=124984edm24暂无昵称, createdTime=Wed Dec 16 12:11:11 CST 2020, time=2020-12-16, status=1, ipAttribution=)]
    2020-12-26 男爵坤

    厉害厉害,

    0

  8. 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16 12:11:11 CST 2020, time=2020-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478052, encodeId=46d414e8052ce, content=<a href='/topic/show?id=bb6f18030a4' target=_blank style='color:#2F92EE;'>#T细胞疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18030, encryptionId=bb6f18030a4, topicName=T细胞疗法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6bea7392214, createdName=124984edm24暂无昵称, createdTime=Wed Dec 16 12:11:11 CST 2020, time=2020-12-16, status=1, ipAttribution=)]
    2020-12-21 慕尔

    噬血细胞综合征会不会有效呢

    0

  9. 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