Cell子刊:陈斯迪团队利用CRISPR筛选,发现增强CAR-T效果新手段

2022-03-12 中国生物技术网 中国生物技术网

尽管早期的治疗取得了成功,但随着时间的推移,治疗的有效性往往会降低,这已经开始寻找增强T细胞功能的方法。

CAR-T细胞疗法通过将肿瘤检测分子引入T细胞来利用对癌症的免疫反应。在过去十年中,FDA批准了六种CAR-T细胞疗法来治疗B细胞淋巴瘤和多发性骨髓瘤。尽管早期的治疗取得了成功,但随着时间的推移,治疗的有效性往往会降低,这已经开始寻找增强T细胞功能的方法。目前还没有批准的CAR-T细胞疗法来治疗实体瘤。 

2022310日,美国耶鲁大学遗传学副教授陈斯迪团队在 Cell 子刊 Cell Metabolism 上发表了题为:A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy 的研究论文。

该研究利用CRSIPR筛选技术,发现了一种增强攻击肿瘤的T细胞的方法,这一发现不仅有望提高一种有前途的基于细胞的癌症免疫疗法的有效性,而且还将扩大它可以治疗的癌症数量。

陈斯迪实验室设计了一种巧妙的方法,可以有效地扫描CD8 T细胞的基因组,并无偏见地识别(寻找)可能增强其功能的基因。

我们开发了一种新的全基因组功能增益筛查,以发现这样的分子酶,它的作用就像踩油门一样,可以增加T细胞的代谢活动,陈教授说。

他们发现了几种基因的高活性,包括PRODH2,在三种不同类型癌症的小鼠模型中刺激CAR-T细胞活性的增加,包括实体瘤乳腺癌。这提供了一种生产超代谢CAR-T细胞的新方法,优于现有的细胞疗法。

利用这些系统和发现,未来的研究可以在临床环境中测试新型代谢增强型CAR-T,识别其他T细胞超级充电器,并扩展到不同的癌症类型,尤其是实体瘤。

耶鲁大学的叶露鹏、Jonathan Park、彭磊和杨全军为论文共同第一作者,陈斯迪为通讯作者。

论文链接:

A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy.Cell Metabolism.https://doi.org/10.1016/j.cmet.2022.02.009

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    2023-02-20 仁者大医
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    2022-08-31 维他命
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    2022-03-14 docwu2019
  5. [GetPortalCommentsPageByObjectIdResponse(id=1781469, encodeId=eede1e8146961, content=<a href='/topic/show?id=8ce8405907' target=_blank style='color:#2F92EE;'>#CAR-#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, 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=Mon Feb 20 11:48:18 CST 2023, time=2023-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1872390, encodeId=4fa018e2390b3, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Jan 15 23:48:18 CST 2023, time=2023-01-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962715, encodeId=31371962e15b9, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Wed Aug 31 02:48:18 CST 2022, time=2022-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1276196, encodeId=d08512e619612, content=<a href='/topic/show?id=755d5211a0' target=_blank style='color:#2F92EE;'>#CRISPR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5211, encryptionId=755d5211a0, topicName=CRISPR)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Mon Mar 14 10:48:18 CST 2022, time=2022-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1584470, encodeId=49e815844e0fb, content=<a href='/topic/show?id=9bbee5948f0' target=_blank style='color:#2F92EE;'>#筛选#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75948, encryptionId=9bbee5948f0, topicName=筛选)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=39da17047364, createdName=ms6747015003810650, createdTime=Mon Mar 14 10:48:18 CST 2022, time=2022-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1202135, encodeId=88501202135f9, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Sat Mar 12 23:45:43 CST 2022, time=2022-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1202093, encodeId=227c120209304, content=👍👍👍👍👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200615/2632ad9b0cbe41099afc78cc410e4829/a6c809eee225447c99a44260c2c470ae.jpg, createdBy=27dc5388613, createdName=ms4000000194031466, createdTime=Sat Mar 12 21:57:50 CST 2022, time=2022-03-12, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1781469, encodeId=eede1e8146961, content=<a href='/topic/show?id=8ce8405907' target=_blank style='color:#2F92EE;'>#CAR-#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, 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=Mon Feb 20 11:48:18 CST 2023, time=2023-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1872390, encodeId=4fa018e2390b3, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Jan 15 23:48:18 CST 2023, time=2023-01-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962715, encodeId=31371962e15b9, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Wed Aug 31 02:48:18 CST 2022, time=2022-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1276196, encodeId=d08512e619612, content=<a href='/topic/show?id=755d5211a0' target=_blank style='color:#2F92EE;'>#CRISPR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5211, encryptionId=755d5211a0, topicName=CRISPR)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Mon Mar 14 10:48:18 CST 2022, time=2022-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1584470, encodeId=49e815844e0fb, content=<a href='/topic/show?id=9bbee5948f0' target=_blank style='color:#2F92EE;'>#筛选#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75948, encryptionId=9bbee5948f0, topicName=筛选)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=39da17047364, createdName=ms6747015003810650, createdTime=Mon Mar 14 10:48:18 CST 2022, time=2022-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1202135, encodeId=88501202135f9, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Sat Mar 12 23:45:43 CST 2022, time=2022-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1202093, encodeId=227c120209304, content=👍👍👍👍👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200615/2632ad9b0cbe41099afc78cc410e4829/a6c809eee225447c99a44260c2c470ae.jpg, createdBy=27dc5388613, createdName=ms4000000194031466, createdTime=Sat Mar 12 21:57:50 CST 2022, time=2022-03-12, status=1, ipAttribution=)]
    2022-03-12 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

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    2022-03-12 ms4000000194031466

    👍👍👍👍👍

    0

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