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Mol Ther：慢病毒转导的CART-meso在晚期实体癌中的I期研究

2020-10-01 MedSci原创 MedSci原创

CART-meso
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本项I期研究调查了慢病毒转导的嵌合抗原受体（CAR）修饰的自体T细胞重定向抗间皮素（CART-meso）在恶性胸膜间皮瘤、卵巢癌和胰腺导管腺癌患者中的安全性和活性。

本项I期研究调查了慢病毒转导的嵌合抗原受体（CAR）修饰的自体T细胞重定向抗间皮素（CART-meso）在恶性胸膜间皮瘤、卵巢癌和胰腺导管腺癌患者中的安全性和活性。

15名化疗难治性癌症患者（每个适应症n = 5名）接受了单次CART-meso细胞输注治疗。通过慢病毒转导，用由抗小鼠间皮素单链可变片段组成的构建体对CART-meso细胞进行了工程改造，该片段衍生自与4-1BB和CD3zeta的细胞内信号域融合的小鼠单克隆抗体SS1。患者接受1-3×107或1-3×108个CART-meso细胞/m2，加或不加1.5g/m2环磷酰胺。

 

结果显示，慢病毒转导的CART-meso细胞耐受性良好；1-3×107/m2的CART-meso在不使用环磷酰胺的情况下发生了一次剂量限制性毒性（4级，败血症）。最佳的总体反应是疾病稳定（11/15名患者）。CART-meso细胞在血液中扩增，并在第6-14天达到峰值水平，但持续时间短暂。环磷酰胺预处理增强了CART-meso的扩增，但没有改善28天后的持续性。在7/10的肿瘤活检中检测到CART-meso DNA。在8/14名患者的血液中检测到人抗嵌合抗体（HACA）。

 

综上所述，该研究结果表明，CART-meso细胞在所有患者的血液中都有良好的耐受性和扩增性，但显示出有限的临床活性。目前评估全人抗甲状腺素CAR的研究正在进行中。

 

原始出处：

 

Andrew R Haas, Janos L Tanyi, et al., Phase I Study of Lentiviral-Transduced Chimeric Antigen Receptor-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers. Mol Ther. 2019 Nov 6;27(11):1919-1929. doi: 10.1016/j.ymthe.2019.07.015. 

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    2020-10-02 zhaojie88

    #ART#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1357604, encodeId=b103135e60471, content=<a href='/topic/show?id=b0702e84b9' target=_blank style='color:#2F92EE;'>#ART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2784, encryptionId=b0702e84b9, topicName=ART)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1401555, encodeId=b33614015559d, content=<a href='/topic/show?id=b9c853e521b' target=_blank style='color:#2F92EE;'>#慢病毒#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53752, encryptionId=b9c853e521b, topicName=慢病毒)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c9bf2348479, createdName=ymljack, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1477268, encodeId=33ef14e726828, content=<a href='/topic/show?id=429a41149d' target=_blank style='color:#2F92EE;'>#cART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4114, encryptionId=429a41149d, topicName=cART)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=46987366013, createdName=ms2999106592497887, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1493302, encodeId=d907149330224, content=<a href='/topic/show?id=4223e0260a' target=_blank style='color:#2F92EE;'>#ESO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7026, encryptionId=4223e0260a, topicName=ESO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=30f59021057, createdName=hongbochen, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1590811, encodeId=de7e1590811ba, content=<a href='/topic/show?id=0c0b115e4cf' target=_blank style='color:#2F92EE;'>#MES#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11574, encryptionId=0c0b115e4cf, topicName=MES)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=874617863969, createdName=longqijun254, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=)]
    2020-10-02 ymljack

    #慢病毒#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1357604, encodeId=b103135e60471, content=<a href='/topic/show?id=b0702e84b9' target=_blank style='color:#2F92EE;'>#ART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2784, encryptionId=b0702e84b9, topicName=ART)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1401555, encodeId=b33614015559d, content=<a href='/topic/show?id=b9c853e521b' target=_blank style='color:#2F92EE;'>#慢病毒#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53752, encryptionId=b9c853e521b, topicName=慢病毒)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c9bf2348479, createdName=ymljack, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1477268, encodeId=33ef14e726828, content=<a href='/topic/show?id=429a41149d' target=_blank style='color:#2F92EE;'>#cART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4114, encryptionId=429a41149d, topicName=cART)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=46987366013, createdName=ms2999106592497887, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1493302, encodeId=d907149330224, content=<a href='/topic/show?id=4223e0260a' target=_blank style='color:#2F92EE;'>#ESO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7026, encryptionId=4223e0260a, topicName=ESO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=30f59021057, createdName=hongbochen, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1590811, encodeId=de7e1590811ba, content=<a href='/topic/show?id=0c0b115e4cf' target=_blank style='color:#2F92EE;'>#MES#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11574, encryptionId=0c0b115e4cf, topicName=MES)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=874617863969, createdName=longqijun254, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=)]
    2020-10-02 ms2999106592497887

    #cART#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1357604, encodeId=b103135e60471, content=<a href='/topic/show?id=b0702e84b9' target=_blank style='color:#2F92EE;'>#ART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2784, encryptionId=b0702e84b9, topicName=ART)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1401555, encodeId=b33614015559d, content=<a href='/topic/show?id=b9c853e521b' target=_blank style='color:#2F92EE;'>#慢病毒#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53752, encryptionId=b9c853e521b, topicName=慢病毒)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c9bf2348479, createdName=ymljack, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1477268, encodeId=33ef14e726828, content=<a href='/topic/show?id=429a41149d' target=_blank style='color:#2F92EE;'>#cART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4114, encryptionId=429a41149d, topicName=cART)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=46987366013, createdName=ms2999106592497887, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1493302, encodeId=d907149330224, content=<a href='/topic/show?id=4223e0260a' target=_blank style='color:#2F92EE;'>#ESO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7026, encryptionId=4223e0260a, topicName=ESO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=30f59021057, createdName=hongbochen, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1590811, encodeId=de7e1590811ba, content=<a href='/topic/show?id=0c0b115e4cf' target=_blank style='color:#2F92EE;'>#MES#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11574, encryptionId=0c0b115e4cf, topicName=MES)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=874617863969, createdName=longqijun254, createdTime=Fri Oct 02 16:24:57 CST 2020, time=2020-10-02, status=1, ipAttribution=)]
    2020-10-02 hongbochen

    #ESO#

    0

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    2020-10-02 longqijun254

    #MES#

    0