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AJOG：CD70抗体-药物偶联剂有望成为子宫平滑肌肉瘤的靶向药

2020-09-03 MedSci原创 MedSci原创

子宫平滑肌肉瘤抗CD70抗体抗体-药物偶联物（ADC）
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子宫平滑肌肉瘤是一种罕见的侵略性的妇科恶性肿瘤，起源于子宫体的子宫肌层，在手术完全切除后仍有很高的复发风险。目前的药物对子宫平滑肌肉瘤只有中等程度的作用。抗体和抗体-药物偶联物（ADC）已被公认为是其

子宫平滑肌肉瘤是一种罕见的侵略性的妇科恶性肿瘤，起源于子宫体的子宫肌层，在手术完全切除后仍有很高的复发风险。目前的药物对子宫平滑肌肉瘤只有中等程度的作用。抗体和抗体-药物偶联物（ADC）已被公认为是其他癌症的有效靶向疗法，但尚无研究评估这种方法对子宫平滑肌肉瘤的作用。

本研究旨在研究子宫平滑肌肉瘤中CD70肿瘤簇的活性，并评估CD70-ADC治疗子宫平滑肌肉瘤的抗肿瘤活性。研究人员首先通过对比分析三种子宫平滑肌肉瘤细胞系（SK-UT-1，SK-LMS-1和SKN）和正常子宫肌层细胞的膜蛋白表达来筛选目标膜蛋白。然后用多种方法检测了膜蛋白CD70在子宫平滑肌肉瘤细胞系和临床样本中的表达水平。最后开发了一种目标膜蛋白的单克隆抗体与单甲基澳瑞他汀F（MMAF）相偶联的ADC，并研究了其对子宫平滑肌肉瘤的抗肿瘤作用。

经鉴定，CD70是子宫平滑肌肉瘤细胞系中高表达的特异性抗原。在三种子宫平滑肌肉瘤细胞系中，通过Western印迹和荧光激活细胞分选分析证实了SK-LMS-1细胞中的CD70表达。在90.5%（19/21）的临床样本中观察到了CD70过表达。

（CD70-ADC处理对移植瘤小鼠模型肿瘤体积的影响）

研究人员将抗CD70单克隆抗体与MMAF的新型衍生物偶联产生了CD70-ADC。CD70-ADC对SK-LMS-1细胞具有显著的抗肿瘤作用（IC50为0.120 nM），但对CD70阴性的子宫平滑肌肉瘤细胞系则无抗肿瘤作用。在SK-LMS-1异种移植小鼠模型和患者来源肿瘤移植模型中，CD70-ADC均可明显抑制肿瘤的生长（肿瘤体积：129.8 vs 285.5 mm3、128.1 vs 837.7 mm3）。


子宫平滑肌肉瘤高表达CD70，用CD70-ADC靶向治疗子宫平滑肌肉瘤或可获得不错的治疗效果。

原始出处：

Rurio Nakae, et al. CD70 antibody-drug conjugate as a potential therapeutic agent for uterine leiomyosarcoma. American Journal of Obstetrics & Gynecology. August 18, 2020.

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1691732, encodeId=8a7e1691e32d4, content=<a href='/topic/show?id=8ed9488e37e' target=_blank style='color:#2F92EE;'>#平滑肌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48873, encryptionId=8ed9488e37e, topicName=平滑肌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a5d29283334, createdName=shijzhiewnjhch, createdTime=Wed Oct 21 15:51:18 CST 2020, time=2020-10-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=892766, encodeId=016d892e66b6, content=好资源, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f2fa5415478, createdName=ms6000001619456004, createdTime=Sun Oct 18 08:59:27 CST 2020, time=2020-10-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885182, encodeId=fdbc88518269, content=<a href='/topic/show?id=85de5518160' target=_blank style='color:#2F92EE;'>#抗体偶联药物#</a>可能是未来的研发重点之一, beContent=null, objectType=article, channel=null, level=null, likeNumber=161, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55181, encryptionId=85de5518160, topicName=抗体偶联药物)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Mon Sep 14 15:50:10 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882467, encodeId=021988246e10, content=<a href='/topic/show?id=0ad110386294' target=_blank style='color:#2F92EE;'>#CD70#</a>作为一个新靶点，值得探索，除掉在<a href='/topic/show?id=3d39451e4bb' target=_blank style='color:#2F92EE;'>#子宫平滑肌肉瘤#</a>中外，其它肿瘤同样值得尝试, beContent=null, objectType=article, channel=null, level=null, likeNumber=126, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103862, encryptionId=0ad110386294, topicName=CD70), TopicDto(id=45174, encryptionId=3d39451e4bb, topicName=子宫平滑肌肉瘤)], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/01/13/dc2daedd2690b46dd6d059a772da6ba3.jpg, createdBy=f0f41699279, createdName=1381abdab4m, createdTime=Thu Sep 03 14:02:40 CST 2020, time=2020-09-03, status=1, ipAttribution=)]
    2020-10-21 shijzhiewnjhch

    #平滑肌#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1691732, encodeId=8a7e1691e32d4, content=<a href='/topic/show?id=8ed9488e37e' target=_blank style='color:#2F92EE;'>#平滑肌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48873, encryptionId=8ed9488e37e, topicName=平滑肌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a5d29283334, createdName=shijzhiewnjhch, createdTime=Wed Oct 21 15:51:18 CST 2020, time=2020-10-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=892766, encodeId=016d892e66b6, content=好资源, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f2fa5415478, createdName=ms6000001619456004, createdTime=Sun Oct 18 08:59:27 CST 2020, time=2020-10-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885182, encodeId=fdbc88518269, content=<a href='/topic/show?id=85de5518160' target=_blank style='color:#2F92EE;'>#抗体偶联药物#</a>可能是未来的研发重点之一, beContent=null, objectType=article, channel=null, level=null, likeNumber=161, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55181, encryptionId=85de5518160, topicName=抗体偶联药物)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Mon Sep 14 15:50:10 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882467, encodeId=021988246e10, content=<a href='/topic/show?id=0ad110386294' target=_blank style='color:#2F92EE;'>#CD70#</a>作为一个新靶点，值得探索，除掉在<a href='/topic/show?id=3d39451e4bb' target=_blank style='color:#2F92EE;'>#子宫平滑肌肉瘤#</a>中外，其它肿瘤同样值得尝试, beContent=null, objectType=article, channel=null, level=null, likeNumber=126, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103862, encryptionId=0ad110386294, topicName=CD70), TopicDto(id=45174, encryptionId=3d39451e4bb, topicName=子宫平滑肌肉瘤)], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/01/13/dc2daedd2690b46dd6d059a772da6ba3.jpg, createdBy=f0f41699279, createdName=1381abdab4m, createdTime=Thu Sep 03 14:02:40 CST 2020, time=2020-09-03, status=1, ipAttribution=)]
    2020-10-18 ms6000001619456004

    好资源

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1691732, encodeId=8a7e1691e32d4, content=<a href='/topic/show?id=8ed9488e37e' target=_blank style='color:#2F92EE;'>#平滑肌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48873, encryptionId=8ed9488e37e, topicName=平滑肌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a5d29283334, createdName=shijzhiewnjhch, createdTime=Wed Oct 21 15:51:18 CST 2020, time=2020-10-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=892766, encodeId=016d892e66b6, content=好资源, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f2fa5415478, createdName=ms6000001619456004, createdTime=Sun Oct 18 08:59:27 CST 2020, time=2020-10-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885182, encodeId=fdbc88518269, content=<a href='/topic/show?id=85de5518160' target=_blank style='color:#2F92EE;'>#抗体偶联药物#</a>可能是未来的研发重点之一, beContent=null, objectType=article, channel=null, level=null, likeNumber=161, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55181, encryptionId=85de5518160, topicName=抗体偶联药物)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Mon Sep 14 15:50:10 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882467, encodeId=021988246e10, content=<a href='/topic/show?id=0ad110386294' target=_blank style='color:#2F92EE;'>#CD70#</a>作为一个新靶点，值得探索，除掉在<a href='/topic/show?id=3d39451e4bb' target=_blank style='color:#2F92EE;'>#子宫平滑肌肉瘤#</a>中外，其它肿瘤同样值得尝试, beContent=null, objectType=article, channel=null, level=null, likeNumber=126, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103862, encryptionId=0ad110386294, topicName=CD70), TopicDto(id=45174, encryptionId=3d39451e4bb, topicName=子宫平滑肌肉瘤)], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/01/13/dc2daedd2690b46dd6d059a772da6ba3.jpg, createdBy=f0f41699279, createdName=1381abdab4m, createdTime=Thu Sep 03 14:02:40 CST 2020, time=2020-09-03, status=1, ipAttribution=)]
    2020-09-14 lovetcm

    #抗体偶联药物#可能是未来的研发重点之一

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1691732, encodeId=8a7e1691e32d4, content=<a href='/topic/show?id=8ed9488e37e' target=_blank style='color:#2F92EE;'>#平滑肌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48873, encryptionId=8ed9488e37e, topicName=平滑肌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a5d29283334, createdName=shijzhiewnjhch, createdTime=Wed Oct 21 15:51:18 CST 2020, time=2020-10-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=892766, encodeId=016d892e66b6, content=好资源, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f2fa5415478, createdName=ms6000001619456004, createdTime=Sun Oct 18 08:59:27 CST 2020, time=2020-10-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885182, encodeId=fdbc88518269, content=<a href='/topic/show?id=85de5518160' target=_blank style='color:#2F92EE;'>#抗体偶联药物#</a>可能是未来的研发重点之一, beContent=null, objectType=article, channel=null, level=null, likeNumber=161, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55181, encryptionId=85de5518160, topicName=抗体偶联药物)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Mon Sep 14 15:50:10 CST 2020, time=2020-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882467, encodeId=021988246e10, content=<a href='/topic/show?id=0ad110386294' target=_blank style='color:#2F92EE;'>#CD70#</a>作为一个新靶点，值得探索，除掉在<a href='/topic/show?id=3d39451e4bb' target=_blank style='color:#2F92EE;'>#子宫平滑肌肉瘤#</a>中外，其它肿瘤同样值得尝试, beContent=null, objectType=article, channel=null, level=null, likeNumber=126, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103862, encryptionId=0ad110386294, topicName=CD70), TopicDto(id=45174, encryptionId=3d39451e4bb, topicName=子宫平滑肌肉瘤)], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/01/13/dc2daedd2690b46dd6d059a772da6ba3.jpg, createdBy=f0f41699279, createdName=1381abdab4m, createdTime=Thu Sep 03 14:02:40 CST 2020, time=2020-09-03, status=1, ipAttribution=)]
    2020-09-03 1381abdab4m

    #CD70#作为一个新靶点，值得探索，除掉在#子宫平滑肌肉瘤#中外，其它肿瘤同样值得尝试

    0

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