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J CLIN INVEST：基因修饰干细胞疗法治疗免疫缺陷性疾病的临床效果评价

2017-03-28 MedSci MedSci原创

免疫缺陷性疾病干细胞
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腺苷脱氨酶缺乏型严重联合免疫缺陷（也称为ADA-SCID或气泡性婴儿疾病）是由遗传突变引起的，导致缺乏腺苷脱氨酶，其是免疫系统的重要组成部分。没有酶，免疫细胞不能抵抗感染。患有疾病的儿童必须在干净无害的环境中保持隔离，以避免接触病毒和细菌; 即使是轻微的感冒也可能是致命的。

近日，来自伦敦大学学院大卫格芬医学院微生物学、免疫学和分子遗传学的研究人员报道了一项关于基因修饰干细胞疗法治疗免疫缺陷性疾病的临床效果评价的研究，相关研究成果刊登于国际杂志J CLIN INVEST上。

腺苷脱氨酶缺乏型严重联合免疫缺陷（也称为ADA-SCID或气泡性婴儿疾病）是由遗传突变引起的，导致缺乏腺苷脱氨酶，其是免疫系统的重要组成部分。没有酶，免疫细胞不能抵抗感染。患有疾病的儿童必须在干净无害的环境中保持隔离，以避免接触病毒和细菌; 即使是轻微的感冒也可能是致命的。

研究人员使用了一种通过遗传修饰每个患者自身造血干细胞来修正ADA-SCID突变的策略，其可以产生所有血细胞类型。在试验中，通过插入负责制备腺苷脱氨酶的基因，在实验室中校正从每个孩子的骨髓中除去的血液干细胞。然后每个孩子接受了自己的修正后的血液干细胞的移植。在2009年至2012年之间招募了10名确诊的ADA缺陷型SCID和无可匹配的同胞或家族供体的受试者，并接受了用人ADA cDNA（MND-ADA）γ逆转录病毒载体修饰后的自体造血CD34 +细胞的移植与白消安（90 mg / m 2）和ERT。在数据分析的时候，追踪从33个月到84个月的受试者。通过记录不良事件的数量来评估手术的安全性。通过测量基因修饰的造血干细胞/祖细胞的移植，ADA基因表达和免疫重建来评估功效。

除了年纪最大的受试者（15岁被招募）外，所有受试者均保留ERT标准化的外周血单个核细胞（PBMC）ADA活性，改善的淋巴细胞数和对促分裂原的正常增殖反应。九个受试者中的三个能够中止静脉注射免疫球蛋白替代治疗。通过最近随访发现，仍能在PBMCs（载体拷贝数[VCN] = 0.1-2.6）和粒细胞（VCN = 0.01-0.3）中持续检测MND-ADA载体。移植后没有患者出现白细胞增生性疾病或其他载体相关的临床并发症。

研究结果证明了对ADA缺陷型SCID进行基因治疗的临床疗效，且具有良好的临床安全性。

原始出处：

Kit L. Shaw, Elizabeth Garabedian, Suparna Mishra. et al. Clinical efficacy of gene-modified stem cells in adenosine deaminase–deficient immunodeficiency.J CLIN INVEST.March 27, 2017.

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    2018-01-06 xiangyuzhou971

    #EST#

    0

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    2017-03-30 jjjiang0199

    #干细胞疗法#

    0

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    2017-03-30 huagfeg

    #评价#

    0

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    2017-03-30 12498d2fm53(暂无昵称)

    #临床效果#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2050627, encodeId=f5dc205062e6b, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Sat Jan 06 02:51:00 CST 2018, time=2018-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1314462, encodeId=51031314462bf, content=<a href='/topic/show?id=4c6348e80a9' target=_blank style='color:#2F92EE;'>#干细胞疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48780, encryptionId=4c6348e80a9, topicName=干细胞疗法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5319428, createdName=jjjiang0199, createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1444197, encodeId=d3fe144419e79, content=<a href='/topic/show?id=3d9291459d1' target=_blank style='color:#2F92EE;'>#评价#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91459, encryptionId=3d9291459d1, topicName=评价)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1fee5134542, createdName=huagfeg, createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1484479, encodeId=8e1914844e9d6, content=<a href='/topic/show?id=889e2284233' target=_blank style='color:#2F92EE;'>#临床效果#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22842, encryptionId=889e2284233, topicName=临床效果)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9fab7968641, createdName=12498d2fm53(暂无昵称), createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1488958, encodeId=de6114889587f, 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=30, 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=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569285, encodeId=aac3156928554, content=<a href='/topic/show?id=1c562e42646' target=_blank style='color:#2F92EE;'>#修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27426, encryptionId=1c562e42646, topicName=修饰)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=29c615505859, createdName=zhangyxzsh, createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1599932, encodeId=f6861599932a7, content=<a href='/topic/show?id=7a7d4168e3a' target=_blank style='color:#2F92EE;'>#基因修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41687, encryptionId=7a7d4168e3a, topicName=基因修饰)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=069c18767911, createdName=apoenzyme, createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=)]
    2017-03-30 rebeccajiejie

    #免疫缺陷#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2050627, encodeId=f5dc205062e6b, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Sat Jan 06 02:51:00 CST 2018, time=2018-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1314462, encodeId=51031314462bf, content=<a href='/topic/show?id=4c6348e80a9' target=_blank style='color:#2F92EE;'>#干细胞疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48780, encryptionId=4c6348e80a9, topicName=干细胞疗法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5319428, createdName=jjjiang0199, createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1444197, encodeId=d3fe144419e79, content=<a href='/topic/show?id=3d9291459d1' target=_blank style='color:#2F92EE;'>#评价#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91459, encryptionId=3d9291459d1, topicName=评价)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1fee5134542, createdName=huagfeg, createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1484479, encodeId=8e1914844e9d6, content=<a href='/topic/show?id=889e2284233' target=_blank style='color:#2F92EE;'>#临床效果#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22842, encryptionId=889e2284233, topicName=临床效果)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9fab7968641, createdName=12498d2fm53(暂无昵称), createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1488958, encodeId=de6114889587f, 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=30, 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=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569285, encodeId=aac3156928554, content=<a href='/topic/show?id=1c562e42646' target=_blank style='color:#2F92EE;'>#修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27426, encryptionId=1c562e42646, topicName=修饰)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=29c615505859, createdName=zhangyxzsh, createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1599932, encodeId=f6861599932a7, content=<a href='/topic/show?id=7a7d4168e3a' target=_blank style='color:#2F92EE;'>#基因修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41687, encryptionId=7a7d4168e3a, topicName=基因修饰)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=069c18767911, createdName=apoenzyme, createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=)]
    2017-03-30 zhangyxzsh

    #修饰#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=2050627, encodeId=f5dc205062e6b, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Sat Jan 06 02:51:00 CST 2018, time=2018-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1314462, encodeId=51031314462bf, content=<a href='/topic/show?id=4c6348e80a9' target=_blank style='color:#2F92EE;'>#干细胞疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48780, encryptionId=4c6348e80a9, topicName=干细胞疗法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5319428, createdName=jjjiang0199, createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1444197, encodeId=d3fe144419e79, content=<a href='/topic/show?id=3d9291459d1' target=_blank style='color:#2F92EE;'>#评价#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91459, encryptionId=3d9291459d1, topicName=评价)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1fee5134542, createdName=huagfeg, createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1484479, encodeId=8e1914844e9d6, content=<a href='/topic/show?id=889e2284233' target=_blank style='color:#2F92EE;'>#临床效果#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22842, encryptionId=889e2284233, topicName=临床效果)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9fab7968641, createdName=12498d2fm53(暂无昵称), createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1488958, encodeId=de6114889587f, 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=30, 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=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569285, encodeId=aac3156928554, content=<a href='/topic/show?id=1c562e42646' target=_blank style='color:#2F92EE;'>#修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27426, encryptionId=1c562e42646, topicName=修饰)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=29c615505859, createdName=zhangyxzsh, createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1599932, encodeId=f6861599932a7, content=<a href='/topic/show?id=7a7d4168e3a' target=_blank style='color:#2F92EE;'>#基因修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41687, encryptionId=7a7d4168e3a, topicName=基因修饰)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=069c18767911, createdName=apoenzyme, createdTime=Thu Mar 30 10:51:00 CST 2017, time=2017-03-30, status=1, ipAttribution=)]
    2017-03-30 apoenzyme

    #基因修饰#

    0