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Blood：放射元素At-211或可消除MM的微小残留病灶

2019-08-09 医刀 MedSci原创

At-211多发性骨髓瘤微小残留病灶CD38
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微小残留病(MRD)在多发性骨髓瘤(MM)中日益普遍和重要。虽然对一线治疗的反应不断加深，但大约75%的MM患者从未取得MRD阴性(≤10-5）；MRD阴性状态预示患者存活期长。MM具有高度异质性，MRD持续存在提示患者体内有分离的单细胞和小簇对治疗耐药的亚克隆存在。几乎所有的MM克隆都对放疗敏感；释放α射线的砹-211(211At)在三细胞直径范围内可释放大量的能量，如果可以有效的靶向，则会是消

微小残留病(MRD)在多发性骨髓瘤(MM)中日益普遍和重要。虽然对一线治疗的反应不断加深，但大约75%的MM患者从未取得MRD阴性(≤10-5）；MRD阴性状态预示患者存活期长。

MM具有高度异质性，MRD持续存在提示患者体内有分离的单细胞和小簇对治疗耐药的亚克隆存在。几乎所有的MM克隆都对放疗敏感；释放α射线的砹-211(211At)在三细胞直径范围内可释放大量的能量，如果可以有效的靶向，则会是消除MRD的理想方法。

CD38是一个已证实的MM靶点，研究人员将211At与抗CD38单克隆抗体结合，创造了一种211At -CD38疗法。研究人员在MM的实体移植瘤模型中检验211At-CD38的效果发现，单剂量211At-CD38（15-45μCi）时，至少可将小鼠的中位存活期延长至对照组的两倍，但没有小鼠获得完全缓解，在75天内全部死亡。

相反，在旨在反映低MRD负荷的扩散疾病模型中，单剂211At-CD38(24-45μCi)可使50-80%的小鼠获得持续的缓解和长期的存活(150天)，而未经处理的小鼠死于20-55天。治疗的毒副反应小而短暂。

综上所述，本研究表明211At-CD38或可消除低疾病负荷背景下的残留MM细胞克隆，包括MRD。研究人员推荐在临床试验的自体干细胞移植（ASCT）调理方案中加入211At-CD38，或可改善MM患者预后。

原始出处：

Shyril O'Steen， et al.The Alpha Emitter Astatine-211 Targeted to CD38 can Eradicate Multiple Myeloma in a Disseminated Disease Model. Blood 2019 ：blood.2019001250； doi： https：//doi.org/10.1182/blood.2019001250

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    2019-12-13 xfpan12

    #At-211#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1780232, encodeId=78041e8023204, content=<a href='/topic/show?id=e1ab2913fb' target=_blank style='color:#2F92EE;'>#At-211#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2913, encryptionId=e1ab2913fb, topicName=At-211)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6bcd409, createdName=xfpan12, createdTime=Fri Dec 13 13:35:00 CST 2019, time=2019-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=371108, encodeId=6b0b3e110883, content=学习了，谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Sun Aug 11 17:13:16 CST 2019, time=2019-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1513029, encodeId=97eb151302982, content=<a href='/topic/show?id=a85c50596d1' target=_blank style='color:#2F92EE;'>#微小残留病灶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50596, encryptionId=a85c50596d1, topicName=微小残留病灶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bbf510523260, createdName=ms3323097325231039, createdTime=Sun Aug 11 11:35:00 CST 2019, time=2019-08-11, status=1, ipAttribution=)]
    2019-08-11 1209e435m98(暂无昵称)

    学习了，谢谢分享

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1780232, encodeId=78041e8023204, content=<a href='/topic/show?id=e1ab2913fb' target=_blank style='color:#2F92EE;'>#At-211#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2913, encryptionId=e1ab2913fb, topicName=At-211)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6bcd409, createdName=xfpan12, createdTime=Fri Dec 13 13:35:00 CST 2019, time=2019-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=371108, encodeId=6b0b3e110883, content=学习了，谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Sun Aug 11 17:13:16 CST 2019, time=2019-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1513029, encodeId=97eb151302982, content=<a href='/topic/show?id=a85c50596d1' target=_blank style='color:#2F92EE;'>#微小残留病灶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50596, encryptionId=a85c50596d1, topicName=微小残留病灶)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bbf510523260, createdName=ms3323097325231039, createdTime=Sun Aug 11 11:35:00 CST 2019, time=2019-08-11, status=1, ipAttribution=)]
    2019-08-11 ms3323097325231039

    #微小残留病灶#

    0