Blood:腺苷脱氨酶重度联合免疫缺陷(ADA SCID)患者基因治疗后的长期预后

2021-06-12 Nebula MedSci原创

基因疗法对ADA SCID患者具有持久的疗效

中心点

基因治疗的效果可稳定长达11年。但根据移植的基因矫正干细胞的水平,结果会有所不同

整合位点分析显示,一些显著的克隆整合到了原癌基因附近的染色体上,但没有导致临床显著的克隆增殖

缺乏功能性腺苷脱氨酶活性的患者会出现严重的联合免疫缺陷(ADA SCID),可以采用ADA酶替代疗法(ERT)、异基因造血干细胞移植(HSCT)或带有基因纠正细胞的自体HSCT(基因疗法-GT)治疗

一个招募了10名3个月-15岁的ADA SCID患者的队列,于2009年-2012年在一项II期临床试验中接受了GT治疗。在体外,给自体骨髓CD34+细胞转导了MND-ADA γ-逆转录病毒载体(gRV),然后输回经过低强度白消安(Busulfan)调节后的患者体内。

10名患者GT治疗后不同血细胞的计数变化

密切随访了8-11年,10名患者中的9位获得了有效的免疫重建足以预防严重感染,并且不需要挽救性ERT或二次异基因HSCT。最年长的患者,无从GT中获益的证据,在GT后6个月重新开始ERT治疗。截止最后一次随访,9名基因标记和B细胞数量最高的可评估患者中有4名仍未需要使用免疫球蛋白替代治疗

10名患者GT治疗后ADA酶活性和红细胞脱氧腺苷核苷酸的变化

血细胞ADA酶活性和腺嘌呤代谢物正常化以及细胞和体液免疫重建的水平均有广泛的响应。年轻患者和接受高剂量基因标记的CD34+细胞治疗的患者的预后普遍较好。没有患者在GT治疗后发生白质增生事件,即使携带持续显著克隆的载体整合到了原癌基因附近的染色体上。

该长期随访研究结果表明,基因疗法对ADA SCID患者具有持久的疗效,但也存在gRV的遗传毒性风险

原始出处:

Reinhardt Bryanna C,Habib Omar,Shaw Kit L et al. Long-term Outcomes after Gene Therapy for Adenosine Deaminase Severe Combined Immune Deficiency (ADA SCID).[J] .Blood, 2021, https://doi.org/10.1182/blood.2020010260

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    2022-04-22 xlxchina
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    2021-06-20 xugumin
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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=38f15486660, createdName=OO云, createdTime=Sun Jun 13 09:48:37 CST 2021, time=2021-06-13, status=1, ipAttribution=)]
    2021-06-17 ms6000000002490719

    0

  5. 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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=631b8488299, createdName=rebeccajiejie, createdTime=Mon Jun 14 14:04:01 CST 2021, time=2021-06-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=973348, encodeId=19b29e3348f1, content=基因疗法对ada scid患者具有持久的疗效,但也存在风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bd984965877, createdName=1453df99m58暂无昵称, createdTime=Sun Jun 13 21:47:33 CST 2021, time=2021-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=973233, encodeId=e8c99e323389, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, 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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=38f15486660, createdName=OO云, createdTime=Sun Jun 13 09:48:37 CST 2021, time=2021-06-13, status=1, ipAttribution=)]
    2021-06-14 般若傻瓜
  6. 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  7. 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    2021-06-13 1453df99m58暂无昵称

    基因疗法对ada scid患者具有持久的疗效,但也存在风险

    0

  8. 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createdTime=Thu Jun 17 00:12:46 CST 2021, time=2021-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1264775, encodeId=7f361264e755f, content=<a href='/topic/show?id=150f19229c' target=_blank style='color:#2F92EE;'>#ADA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1922, encryptionId=150f19229c, topicName=ADA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad9f79, createdName=般若傻瓜, createdTime=Mon Jun 14 14:04:01 CST 2021, time=2021-06-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1489000, encodeId=6c14148900099, content=<a href='/topic/show?id=7df32913871' target=_blank style='color:#2F92EE;'>#免疫缺陷#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29138, encryptionId=7df32913871, topicName=免疫缺陷)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=631b8488299, createdName=rebeccajiejie, createdTime=Mon Jun 14 14:04:01 CST 2021, time=2021-06-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=973348, encodeId=19b29e3348f1, content=基因疗法对ada scid患者具有持久的疗效,但也存在风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bd984965877, createdName=1453df99m58暂无昵称, createdTime=Sun Jun 13 21:47:33 CST 2021, time=2021-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=973233, encodeId=e8c99e323389, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210613/8ff64d769edb4908984f69562f72ad91/3a42ed970eca477e97b213e0c499699c.jpg, createdBy=cb385520061, createdName=苹果儿, createdTime=Sun Jun 13 10:28:05 CST 2021, time=2021-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=973229, encodeId=24059e3229b4, content=学习了一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/PiajxSqBRaEKXpC8j9TaoCpG4yIB3skibUZ0ricmVQ6KKIVpqYQxINrmlibsPZSia7GOUupzuINf8UITMib8awsjjkPw/0, createdBy=abbf1713451, createdName=zt123, createdTime=Sun Jun 13 10:18:26 CST 2021, time=2021-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=973224, encodeId=c5c39e322450, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=38f15486660, createdName=OO云, createdTime=Sun Jun 13 09:48:37 CST 2021, time=2021-06-13, status=1, ipAttribution=)]
    2021-06-13 苹果儿

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=1991630, encodeId=857b199163063, content=<a href='/topic/show?id=f88a4e047f' target=_blank style='color:#2F92EE;'>#CID#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4704, encryptionId=f88a4e047f, topicName=CID)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=570f404, createdName=xlxchina, createdTime=Fri Apr 22 01:04:01 CST 2022, time=2022-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1645648, encodeId=59ab164564883, content=<a href='/topic/show?id=79d99e04630' target=_blank style='color:#2F92EE;'>#长期预后#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97046, encryptionId=79d99e04630, topicName=长期预后)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0e4823226485, 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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=631b8488299, createdName=rebeccajiejie, createdTime=Mon Jun 14 14:04:01 CST 2021, time=2021-06-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=973348, encodeId=19b29e3348f1, content=基因疗法对ada scid患者具有持久的疗效,但也存在风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bd984965877, createdName=1453df99m58暂无昵称, createdTime=Sun Jun 13 21:47:33 CST 2021, time=2021-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=973233, encodeId=e8c99e323389, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210613/8ff64d769edb4908984f69562f72ad91/3a42ed970eca477e97b213e0c499699c.jpg, createdBy=cb385520061, createdName=苹果儿, createdTime=Sun Jun 13 10:28:05 CST 2021, time=2021-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=973229, encodeId=24059e3229b4, content=学习了一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/PiajxSqBRaEKXpC8j9TaoCpG4yIB3skibUZ0ricmVQ6KKIVpqYQxINrmlibsPZSia7GOUupzuINf8UITMib8awsjjkPw/0, createdBy=abbf1713451, createdName=zt123, createdTime=Sun Jun 13 10:18:26 CST 2021, time=2021-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=973224, encodeId=c5c39e322450, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=38f15486660, createdName=OO云, createdTime=Sun Jun 13 09:48:37 CST 2021, time=2021-06-13, status=1, ipAttribution=)]
    2021-06-13 zt123

    学习了一下

    0

  10. 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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=631b8488299, createdName=rebeccajiejie, createdTime=Mon Jun 14 14:04:01 CST 2021, time=2021-06-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=973348, encodeId=19b29e3348f1, content=基因疗法对ada scid患者具有持久的疗效,但也存在风险, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bd984965877, createdName=1453df99m58暂无昵称, createdTime=Sun Jun 13 21:47:33 CST 2021, time=2021-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=973233, encodeId=e8c99e323389, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, 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attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=38f15486660, createdName=OO云, createdTime=Sun Jun 13 09:48:37 CST 2021, time=2021-06-13, status=1, ipAttribution=)]
    2021-06-13 OO云

    学习了

    0

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