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Cancer Discov.：新型Sym004 抗-EGFR抗体混合物用于难治性结直肠癌的临床研究

2015-05-14 范伟 译 MedSci原创

新型Sym004抗-EGFR抗体混合物结直肠癌
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背景：在表皮生长因子受体（EGFR）抑制剂的抵抗下肿瘤生长可能保持EGFR-依从性，其是通过补偿性的配体上调和新创基因突变进行介导的。Sym004是靶标为非重叠EGFR抗原的两个抗体混合物。临床试验：在临床前模型中，Sym004可使EGFR显著的内化和降解，在配体的存在下转化为更上一级的生长抑制作用。在临床I期试验阶段，剂量升级期间，我们观察到基于机制的剂量限制反应：3级皮肤毒性和低镁血症。在剂量

背景：在表皮生长因子受体（EGFR）抑制剂的抵抗下肿瘤生长可能保持EGFR-依从性，其是通过补偿性的配体上调和新创基因突变进行介导的。Sym004是靶标为非重叠EGFR抗原的两个抗体混合物。


临床试验：在临床前模型中，Sym004可使EGFR显著的内化和降解，在配体的存在下转化为更上一级的生长抑制作用。在临床I期试验阶段，剂量升级期间，我们观察到基于机制的剂量限制反应：3级皮肤毒性和低镁血症。在剂量扩张组每周采用9和12毫克/公斤的Sym004，并招募了转移性结直肠癌患者和获得性表皮生长因子受体抑制剂抵抗的患者；39例患者中的17例(44%)肿瘤治愈，5例患者(13%)达到局部反应。药效的研究证实标记的Sym004-诱导表皮生长因子受体EGFR下调。在Sym004治疗期间1例病人出现MET基因扩增，在EGFRS492R突变患者中观察到部分反应，预测是西妥昔单抗的抵抗。

意义与作用：在转移性结直肠癌患者和获得性耐药西妥昔单抗/ 帕尼单抗患者中Sym004强有效的EGFR下调转化为重要的抗肿瘤活性，验证了一定比例的肿瘤仍然依赖于表皮生长因子受体信号通路这样的临床假设。研究表明二级RAS /EGFR突变反应模式的进一步临床开发和扩展的相关分析是必要的。

原始出处：

Dienstmann R, Patnaik A, GarciaCarbonero R, Cervantes A, Benavent M,et al.Safety and Activity of the First-in-Class Sym004 Anti-EGFR Antibody Mixture in Patients with Refractory Colorectal Cancer.Cancer Discov. 2015 May 11.

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    2016-03-13 cmj8wellington

    #Dis#

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    2015-05-17 huaxipanxing

    看看

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    2015-05-16 crystal0564

    #结直肠#

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    2015-05-16 freve

    #难治性#

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    2015-05-16 liuyiping

    #GFR#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2011987, encodeId=5a0b201198e3c, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Sun Mar 13 00:48:00 CST 2016, time=2016-03-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=23926, encodeId=77b0239266a, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee0d1618732, createdName=huaxipanxing, createdTime=Sun May 17 20:11:00 CST 2015, time=2015-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1452755, encodeId=1d961452e5521, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Sat May 16 03:48:00 CST 2015, time=2015-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1528289, encodeId=e1e4152828976, content=<a href='/topic/show?id=74b798601a1' target=_blank style='color:#2F92EE;'>#难治性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98601, encryptionId=74b798601a1, topicName=难治性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a1ef11916292, createdName=freve, createdTime=Sat May 16 03:48:00 CST 2015, time=2015-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534272, encodeId=ab1a15342e2eb, content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7988, encryptionId=22b3e9887e, topicName=GFR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0a812532020, createdName=liuyiping, createdTime=Sat May 16 03:48:00 CST 2015, time=2015-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1587782, encodeId=4d31158e782ac, content=<a href='/topic/show?id=cb1e1006ebd' target=_blank style='color:#2F92EE;'>#ISC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10067, encryptionId=cb1e1006ebd, topicName=ISC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=173417575755, createdName=yankaienglish, createdTime=Sat May 16 03:48:00 CST 2015, time=2015-05-16, status=1, ipAttribution=)]
    2015-05-16 yankaienglish

    #ISC#

    0