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ASCO2017：联合HDAC和BET抑制剂来提高癌症疫苗诱导的T细胞反应

2017-06-06 zhangfan MedSci原创

癌症疫苗HDACBET
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多种疫苗免疫后，联合HDAC和BET 抑制剂可以显著提高CD8 T细胞应答和B16-OVA抗性

小鼠模型研究表明组蛋白去乙酰化酶（HDAC）联合溴结构域和额外终端域家族蛋白（BET）抑制剂对胰腺导管腺癌，黑色素瘤和淋巴瘤表现出良好的抑制效果。但上述研究并未考虑肿瘤免疫的作用。

近日研究人员将HDAC抑制剂罗米地辛(RMD)，BET抑制剂I-BET151与疫苗联用的效果进行了考察。研究人员首先对C57Bl/6小鼠注射各类免疫疫苗，之后再进行RMD， I-BET151或二联治疗。

研究结果如下：腺病毒疫苗+RMD+I-BET151可显著提高抗原特异性CD8 T细胞的频率和数量；RMD+I-BET151治疗影响的疫苗引起继发性T细胞应答，显着增加的IFN-γ和脾CD8 T细胞频率和保持IFN-γ和TNFα多官能度。CD8 T细胞保持对单核细胞增生李斯特菌的保护能力并可抑制B16 OVA。仅RMD+I-BET151 治疗后调节性T细胞频率和CD4和CD8总细胞数量保持不变。

研究认为，多种疫苗免疫后，联合HDAC和BET 抑制剂可以显著提高CD8 T细胞应答和B16-OVA抗性。

原始出处：

Alexander Badamchi-Zadeh et al. Combined HDAC and BET inhibition to enhance cancer vaccine-elicited T-cell responses. 2017 ASCO Annual Meeting. June 2017.

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    2018-01-29 lingaifan

    #HDAC#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=2003406, encodeId=0e6e200340623, content=<a href='/topic/show?id=86d585931d' target=_blank style='color:#2F92EE;'>#HDAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8593, encryptionId=86d585931d, topicName=HDAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Mon Jan 29 14:00:00 CST 2018, time=2018-01-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1938701, encodeId=aa0c1938e01e2, content=<a href='/topic/show?id=1c292818fd' target=_blank style='color:#2F92EE;'>#ASC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2818, encryptionId=1c292818fd, topicName=ASC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=74808, createdName=quxin068, createdTime=Mon Jul 17 23:00:00 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1759994, encodeId=3fe71e5999415, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Thu Dec 28 12:00:00 CST 2017, time=2017-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1649525, encodeId=8f681649525dd, content=<a href='/topic/show?id=5b05180159a' target=_blank style='color:#2F92EE;'>#T细胞反应#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18015, encryptionId=5b05180159a, topicName=T细胞反应)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cce623855314, createdName=millore, createdTime=Sun Apr 01 13:00:00 CST 2018, time=2018-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1643028, encodeId=e76d1643028d7, content=<a href='/topic/show?id=fb843362b1' target=_blank style='color:#2F92EE;'>#BET抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3362, encryptionId=fb843362b1, topicName=BET抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b14423056177, createdName=循证小兵, createdTime=Sun Oct 15 19:00:00 CST 2017, time=2017-10-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851449, encodeId=fed6185144938, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri Aug 11 01:00:00 CST 2017, time=2017-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=207337, encodeId=c60d20e33781, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib2JlGvwpAibiaovVhfA9DbO7X7JLGGjM4Cic6oMgxLdnuS9piaP9cnG2OwIbkzHvX0qzS1boibyYNqR5vHZu7HQs5EIB/0, createdBy=298d1398341, createdName=lou.minghong, createdTime=Tue Jun 06 13:21:44 CST 2017, time=2017-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=207313, encodeId=74cc20e31339, content=优质资源，共同学习共同进步, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5K0LqDY57Aia0TOQByoJhNt3icm4sfukp500hLH6RHOpFdV01NbECtAV7s0qKpQPibyRukQAwAmqJU3X/0, createdBy=f91f1928792, createdName=九九消寒, createdTime=Tue Jun 06 12:28:09 CST 2017, time=2017-06-06, status=1, ipAttribution=)]
    2017-07-17 quxin068

    #ASC#

    0

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    2017-12-28 ms5439512287675881

    #BET#

    0

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    2018-04-01 millore

    #T细胞反应#

    0

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    2017-10-15 循证小兵

    #BET抑制剂#

    0

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    2017-08-11 jklm09

    #抑制剂#

    0

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    2017-06-06 lou.minghong

    学习

    0

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    2017-06-06 九九消寒

    优质资源，共同学习共同进步

    0

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很多人都是谈癌色变，一旦确诊癌症以后就变得绝望，变得崩溃。不过，当前有一个好消息是，一种名为CMB305的癌症疫苗表现出的效果或比FDA已经批准的癌症药物效果更好，为癌症治疗带来新希望。

Cell Reports：癌症疫苗新型佐剂探索

癌症免疫疗法是目前临床癌症治疗中的新型潮流。FDA最近批准了针对转移性前列腺癌的树突状细胞免疫疗法以及利用免疫抑制阻断型抗体PD-1，CTLA-4的免疫检查点疗法。尽管有这些突破，目前的癌症免疫疗法还是存在诸多限制。比如肿瘤疫苗释放效率低下，肿瘤组织特异性抗原的交叉呈递受阻，一系列的免疫抑制性细胞因子的作用，等等。 先天免疫是抗肿瘤免疫的重要组成部分，因此介导先天免疫与后天免疫的信号分子能够