ASCO2017：NKTR-214促进患者免疫细胞增殖以及PD-1表达

2017-05-20 鱼会飞艾兰博曼医学网

新型IL-2细胞因子免疫激动剂（NKTR-214）是CD122依赖型的激动剂，可以通过异源二聚体IL-2受体途径(IL-2Rβɣ)提供持续的信号转导，还可以在肿瘤卫环境中通过调节性T细胞刺激CD8+ T细胞和NK细胞的增殖。本研究在局部晚期或转移性实体瘤患者中对经过NKTR-214治疗后的肿瘤微环境的免疫变化进行了评估。

新型IL-2细胞因子免疫激动剂（NKTR-214）是CD122依赖型的激动剂，可以通过异源二聚体IL-2受体途径(IL-2Rβɣ)提供持续的信号转导，还可以在肿瘤卫环境中通过调节性T细胞刺激CD8+ T细胞和NK细胞的增殖。本研究在局部晚期或转移性实体瘤患者中对经过NKTR-214治疗后的肿瘤微环境的免疫变化进行了评估。

研究采用以下方法，对IV期的门诊的肿瘤患者进行q2w（两周一次）或q3w（三周一次）的NKTR-214治疗。采集血液和肿瘤组织样品，用流式细胞术、免疫组化（IHC）、T细胞克隆、基因表达分析等方法进行免疫活性的测定。

在三周一次经NKTR-214治疗的26例患者中，接受的治疗剂量分别为4例0.003mg / kg、9例0.006 mg / kg、6例0.009 mg / kg和1例0.012 mg/kg。研究结果表明，二周一次治疗的患者有6例接受0.006 mg/kg的NKTR-214治疗。最常见的Gr1-2 TRAEs为疲劳（73％）、瘙痒（65％）、食欲不振（46%）。1例患者在最高剂量下出现Gr3昏厥和低血压反应，并以较低剂量继续治疗。没有与药物相关的AEs导致研究停止。没有观察到与免疫相关的AE或者毛细血管渗透综合征。6例（23%）的患者肿瘤发生了10-30%的缩小。3例没有接受过免疫治疗的患者在结束NKTR-214治疗后，在接受抗PD-1治疗后肿瘤明显消退。所有患者的血液样品检测治疗8天后新增殖（Ki67 +）T和NK细胞增加。流式细胞术和/或IHC显示肿瘤微环境中肿瘤CD8 + T和NK细胞的基线增加高达10倍，Treg的变化最小。PD-1表达在TIL中增加2倍。肿瘤组织的基因表达分析显示几种免疫检查点基因、细胞毒性标志物(IFNg, PRF1, and GZMB)以及T细胞克隆性都有所增加。

原始出处：

Chantale Bernatchez, Cara L. Haymaker, et al. Effect of a novel IL-2 cytokine immune agonist (NKTR-214) on proliferating CD8+T cells and PD-1 expression on immune cells in the tumor microenvironment in patients with prior checkpoint therapy. 2017 ASCO Annual Meeting Abstract No:2545

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2017-11-02 xuruicheng

#NKT#

44 0
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2017-09-04 quxin068

#ASC#

22 0
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2017-08-07 zhixianchen

#NKTR-214#

32 0
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2017-05-22 晓辰

#细胞增殖#

31 0
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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/21/39b6a0099eb602e8ac1f7e10d5d440a9.jpg, createdBy=dee01724555, createdName=杨利洪, createdTime=Mon May 22 07:14:16 CST 2017, time=2017-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=200985, encodeId=681a200985d7, content=学习有益，谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=550d2008262, createdName=luominglian113, createdTime=Mon May 22 00:02:24 CST 2017, time=2017-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=200745, encodeId=b32a200e45a7, content=非常好的文章，学习了，很受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NdicLmdJEK9VoiaDianY6fzHNN9iaGv80m39pMHU3eSnNN0kn1o0rdQ7Bz2f03Qibcf1ia7rKvxIt4UVlErF2d4gCmDC5/0, createdBy=98e31740255, createdName=cqykthl, createdTime=Sun May 21 07:42:15 CST 2017, time=2017-05-21, status=1, ipAttribution=)]
2017-05-22 ylzr123

感谢小编为我们准备了如此丰盛的精神大餐，同时也向作者致谢！认真学习了，点赞！

62 0
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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NdicLmdJEK9VoiaDianY6fzHNN9iaGv80m39pMHU3eSnNN0kn1o0rdQ7Bz2f03Qibcf1ia7rKvxIt4UVlErF2d4gCmDC5/0, createdBy=98e31740255, createdName=cqykthl, createdTime=Sun May 21 07:42:15 CST 2017, time=2017-05-21, status=1, ipAttribution=)]
2017-05-22 杨利洪

学习并分享了

58 0
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2017-05-22 luominglian113

学习有益，谢谢分享

64 0
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2017-05-21 天涯183

非常好的文章，学习了，很受益

57 0
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2017-05-21 lofter

学习了，感谢分享！

53 0
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2017-05-21 cqykthl

又发现新的标志物，对肿瘤领域又是一个进步

25 0