Nat Commun:GD2-B7H3 SynNotch CAR-T在转移性神经母细胞瘤中的临床前评估

2021-01-26 haibei MedSci原创

GD2-B7H3 CAR-T细胞在体外和转移性异种移植小鼠模型中控制神经母细胞瘤的生长,具有很高的特异性和有效性。

虽然CAR-T细胞治疗B细胞恶性肿瘤的结果是非常令人鼓舞的,但用类似的方法治疗儿童实体瘤的疗效有限。提高CAR-T细胞治疗实体瘤的成功率的障碍是多因素的。肿瘤相关抗原(TAA)的识别与最小的非肿瘤副作用是目前主要的挑战之一。到目前为止,在成人实体瘤中,CAR-T细胞临床试验一直表现出严重的毒性或很少的疗效。

目前利用临床前模型来预测实体瘤中嵌合抗原受体(CAR)T细胞的临床毒性的能力是薄弱的,因此我们需要开发和评估门控系统。最近,研究人员发现小鼠GD2 CAR-T细胞,对肿瘤相关抗原GD2的特异性,以协同调节域依赖的方式诱导致命的神经毒性。

同时,人B7H3 CAR-T细胞在神经母细胞瘤的临床前模型中表现出疗效。为了寻求更好的CAR,研究人员生成了一个SynNotch门控的CAR-T,GD2-B7H3,其识别GD2为门,B7H3为靶。

GD2-B7H3 CAR-T细胞在体外和转移性异种移植小鼠模型中控制神经母细胞瘤的生长,具有很高的特异性和有效性。

这些改进部分来自GD2-B7H3 CAR-T细胞较好的代谢适应性,其naïve T样细胞毒性后的氧化代谢和较低的耗竭情况证明了这一点。

 

原始出处:

Babak Moghimi et al. Preclinical assessment of the efficacy and specificity of GD2-B7H3 SynNotch CAR-T in metastatic neuroblastoma . Nature Communications (2021). 

 

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    2021-06-08 海豹
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    2021-04-05 liuli5079
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encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri Oct 29 10:24:36 CST 2021, time=2021-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1772377, encodeId=92281e72377ea, content=<a href='/topic/show?id=c38963544cc' target=_blank style='color:#2F92EE;'>#母细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=63544, encryptionId=c38963544cc, topicName=母细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b07438375157, createdName=huperzia, createdTime=Fri Jul 30 05:24:36 CST 2021, time=2021-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1373797, encodeId=f95b13e37973d, content=<a href='/topic/show?id=eb3b129e01d' target=_blank style='color:#2F92EE;'>#Notch#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12970, encryptionId=eb3b129e01d, topicName=Notch)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ece5364, createdName=karmond, createdTime=Thu Jan 28 02:24:36 CST 2021, time=2021-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1386696, encodeId=32361386696b6, content=<a href='/topic/show?id=f08293399f9' target=_blank style='color:#2F92EE;'>#转移性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93399, encryptionId=f08293399f9, topicName=转移性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ac22500003, createdName=1249842em09(暂无昵称), createdTime=Thu Jan 28 02:24:36 CST 2021, time=2021-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1476112, encodeId=e93714e61120f, content=<a href='/topic/show?id=2bcee797732' target=_blank style='color:#2F92EE;'>#细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77977, encryptionId=2bcee797732, topicName=细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf5e7252474, createdName=spoonycyy, createdTime=Thu Jan 28 02:24:36 CST 2021, time=2021-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1487497, encodeId=7a91148e497ef, content=<a href='/topic/show?id=ba951352387' target=_blank style='color:#2F92EE;'>#OTC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13523, encryptionId=ba951352387, topicName=OTC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b36f8313624, createdName=ymljack, createdTime=Thu Jan 28 02:24:36 CST 2021, time=2021-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=920210, encodeId=abea92021076, content=神经母细胞瘤, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=1eb15456360, createdName=ms6000000454403523, createdTime=Wed Jan 27 09:13:54 CST 2021, time=2021-01-27, status=1, ipAttribution=)]
    2021-10-29 liye789132251
  5. [GetPortalCommentsPageByObjectIdResponse(id=1795227, encodeId=be121e95227d4, content=<a href='/topic/show?id=23781699020' target=_blank style='color:#2F92EE;'>#synNotch#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16990, encryptionId=23781699020, topicName=synNotch)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3289320, createdName=海豹, createdTime=Tue Jun 08 01:24:36 CST 2021, time=2021-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2087891, encodeId=56d2208e891ea, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Mon Apr 05 11:24:36 CST 2021, time=2021-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1781408, encodeId=5fa61e8140810, content=<a href='/topic/show?id=8ce8405907' target=_blank style='color:#2F92EE;'>#CAR-#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4059, encryptionId=8ce8405907, topicName=CAR-)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Sun Feb 21 00:24:36 CST 2021, time=2021-02-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884931, encodeId=e1a31884931eb, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, 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channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12970, encryptionId=eb3b129e01d, topicName=Notch)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ece5364, createdName=karmond, createdTime=Thu Jan 28 02:24:36 CST 2021, time=2021-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1386696, encodeId=32361386696b6, content=<a href='/topic/show?id=f08293399f9' target=_blank style='color:#2F92EE;'>#转移性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93399, encryptionId=f08293399f9, topicName=转移性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ac22500003, createdName=1249842em09(暂无昵称), createdTime=Thu Jan 28 02:24:36 CST 2021, time=2021-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1476112, encodeId=e93714e61120f, content=<a href='/topic/show?id=2bcee797732' target=_blank style='color:#2F92EE;'>#细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77977, encryptionId=2bcee797732, topicName=细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf5e7252474, createdName=spoonycyy, createdTime=Thu Jan 28 02:24:36 CST 2021, time=2021-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1487497, encodeId=7a91148e497ef, content=<a href='/topic/show?id=ba951352387' target=_blank style='color:#2F92EE;'>#OTC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13523, encryptionId=ba951352387, topicName=OTC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b36f8313624, createdName=ymljack, createdTime=Thu Jan 28 02:24:36 CST 2021, time=2021-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=920210, encodeId=abea92021076, content=神经母细胞瘤, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=1eb15456360, createdName=ms6000000454403523, createdTime=Wed Jan 27 09:13:54 CST 2021, time=2021-01-27, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1795227, encodeId=be121e95227d4, content=<a href='/topic/show?id=23781699020' target=_blank style='color:#2F92EE;'>#synNotch#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16990, encryptionId=23781699020, topicName=synNotch)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3289320, createdName=海豹, createdTime=Tue Jun 08 01:24:36 CST 2021, time=2021-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2087891, encodeId=56d2208e891ea, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, 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encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri Oct 29 10:24:36 CST 2021, time=2021-10-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1772377, encodeId=92281e72377ea, content=<a href='/topic/show?id=c38963544cc' target=_blank style='color:#2F92EE;'>#母细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=63544, encryptionId=c38963544cc, topicName=母细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b07438375157, createdName=huperzia, createdTime=Fri Jul 30 05:24:36 CST 2021, time=2021-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1373797, encodeId=f95b13e37973d, content=<a href='/topic/show?id=eb3b129e01d' target=_blank style='color:#2F92EE;'>#Notch#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12970, encryptionId=eb3b129e01d, topicName=Notch)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ece5364, createdName=karmond, createdTime=Thu Jan 28 02:24:36 CST 2021, time=2021-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1386696, encodeId=32361386696b6, content=<a href='/topic/show?id=f08293399f9' target=_blank style='color:#2F92EE;'>#转移性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93399, encryptionId=f08293399f9, topicName=转移性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ac22500003, createdName=1249842em09(暂无昵称), createdTime=Thu Jan 28 02:24:36 CST 2021, time=2021-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1476112, encodeId=e93714e61120f, content=<a href='/topic/show?id=2bcee797732' target=_blank style='color:#2F92EE;'>#细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77977, encryptionId=2bcee797732, topicName=细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf5e7252474, createdName=spoonycyy, createdTime=Thu Jan 28 02:24:36 CST 2021, time=2021-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1487497, encodeId=7a91148e497ef, content=<a href='/topic/show?id=ba951352387' target=_blank style='color:#2F92EE;'>#OTC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13523, encryptionId=ba951352387, topicName=OTC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b36f8313624, createdName=ymljack, createdTime=Thu Jan 28 02:24:36 CST 2021, time=2021-01-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=920210, encodeId=abea92021076, content=神经母细胞瘤, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=1eb15456360, createdName=ms6000000454403523, createdTime=Wed Jan 27 09:13:54 CST 2021, time=2021-01-27, status=1, ipAttribution=)]
    2021-01-28 karmond
  7. [GetPortalCommentsPageByObjectIdResponse(id=1795227, encodeId=be121e95227d4, content=<a href='/topic/show?id=23781699020' target=_blank style='color:#2F92EE;'>#synNotch#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16990, encryptionId=23781699020, topicName=synNotch)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3289320, createdName=海豹, createdTime=Tue Jun 08 01:24:36 CST 2021, time=2021-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2087891, encodeId=56d2208e891ea, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, 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  8. 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    2021-01-28 ymljack
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    2021-01-27 ms6000000454403523

    神经母细胞瘤

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