PNAS：揭秘CAR-T疗法及副作用路径！有望治疗实体瘤！

2018-02-13 Yui 转化医学网

CAR-T疗法近些年来大热，虽然它目前只能治疗血液系统的疾病，但这并不妨碍人们在其他领域对它的探索。发表在PNAS上的一篇研究揭示了CAR-T及其副作用的机制。这将有助于我们开展对实体瘤的治疗。

CAR-T疗法近些年来大热，虽然它目前只能治疗血液系统的疾病，但这并不妨碍人们在其他领域对它的探索。发表在PNAS上的一篇研究揭示了CAR-T及其副作用的机制。这将有助于我们开展对实体瘤的治疗。

CAR-T细胞疗法是一种新型的免疫治疗形式，它将患者自体的免疫T细胞提出后经过基因改造再重新回输至患者体内，经改造后的免疫T细胞可有效的针对性杀死癌细胞。目前该疗法已经由FDA于2017批准，用于治疗血液系统的肿瘤，如儿童白血病和某些淋巴瘤。

而2月12日发表在《PNAS》,题目为“Intensity and duration of TCR signaling is limited by p38 phosphorylation of ZAP-70T293 and destabilization of the signalosome”的研究揭秘了CAR-T疗法能够快速靶向癌细胞并将其杀死的关键机制，并解释了该疗法为什么会导致严重的副作用。

机体内适应性免疫应答是由T细胞增殖、分化并被激活后发挥效应。其中生理性T细胞的活化主要是通过T细胞受体（TCR）和抗原递呈细胞提供的肽/ MHC复合物共同诱导形成的。

Walter和Eliza Hall医学研究所的Misty Jenkins 博士及其团队通过研究CAR-T细胞如何与癌细胞相互作用中发现了酪氨酸激酶ZAP-70对T细胞抗原受体(TCR)信号的启动具有至关重要的作用。

由TCR信号激活的丝氨酸激酶p38，则直接反过来磷酸化其上游的络氨酸激酶ZAP-70。这一负反馈就会降低TCR信号复合物的大小和寿命，限制了T细胞的免疫反应，破坏了其稳定性。

p38在体外和TCR激活的T细胞中磷酸化ZAP-70

Misty Jenkins博士说：“我们发现CAR-T细胞受体具有快速识别和鉴别那些在免疫系统中仍未被检测到的肿瘤细胞，并立即杀死它们。之前我们就已经证明细胞因子的产生与免疫细胞锁定在癌细胞上的时间有关，细胞接触的时间越长，产生的细胞因子就越多，从而导致炎症的程度越来越高。”

目前Misty Jenkins博士和她的团队正在集中研究如何用CAR-T疗法治疗脑癌。脑癌拥有较差的存活率，并对传统治疗，化疗等有抵抗性，而手术切除也会带来大量的附加伤害。CAR-T治疗或许能为脑癌的治疗提供新的思路。

同时，Misty Jenkins博士在2017年获得了脑癌基金会及儿童基金会的资助，支持她继续开展免疫疗法治疗脑癌患儿。

原始出处:

Maria Letizia Giardino Torchia el al.Intensity and duration of TCR signaling is limited by p38 phosphorylation of ZAP-70T293 and destabilization of the signalosome.PNAS (2018).

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2018-08-06 仁心济世

#CAR-#

66 0
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2018-03-23 showtest

#副作用#

60 0
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2019-01-14 drwjr

#PNAS#

56 0
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2018-03-09 qingfengqishi5

学习了.学习了

75 0
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2018-03-08 qingfengqishi5

学习了.学习了

84 0
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2018-03-07 qingfengqishi5

学习了.学习了

74 0
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2018-03-06 qingfengqishi5

学习了.学习了

102 0
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2018-03-05 qingfengqishi5

学习了.学习了

72 0
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GetPortalCommentsPageByObjectIdResponse(id=293144, encodeId=b5f329314458, content=学习了.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzTetibytbqFDmFITWHyBWbxU7S9MYibgPSqvu0sYteH0N6zXqbU0Kf3Mbdb7yWM1Kud3zPgYBibE2SZ/0, createdBy=da7696924, createdName=qingfengqishi5, createdTime=Mon Mar 05 07:24:51 CST 2018, time=2018-03-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=292996, encodeId=9b55292996ec, content=学习了.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzTetibytbqFDmFITWHyBWbxU7S9MYibgPSqvu0sYteH0N6zXqbU0Kf3Mbdb7yWM1Kud3zPgYBibE2SZ/0, createdBy=da7696924, createdName=qingfengqishi5, createdTime=Sun Mar 04 22:56:42 CST 2018, time=2018-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=288574, encodeId=41fd2885e4ee, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Sat Feb 17 07:38:47 CST 2018, time=2018-02-17, status=1, ipAttribution=)]
2018-03-04 qingfengqishi5

学习了.学习了

44 0
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encryptionId=56a932e7800, topicName=副作用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8f0715, createdName=showtest, createdTime=Fri Mar 23 10:52:00 CST 2018, time=2018-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1856142, encodeId=ae9e185614248, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Mon Jan 14 17:52:00 CST 2019, time=2019-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=294511, encodeId=6d4029451198, content=学习了.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzTetibytbqFDmFITWHyBWbxU7S9MYibgPSqvu0sYteH0N6zXqbU0Kf3Mbdb7yWM1Kud3zPgYBibE2SZ/0, createdBy=da7696924, createdName=qingfengqishi5, createdTime=Fri Mar 09 11:05:52 CST 2018, time=2018-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=294090, encodeId=e1ca29409012, content=学习了.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzTetibytbqFDmFITWHyBWbxU7S9MYibgPSqvu0sYteH0N6zXqbU0Kf3Mbdb7yWM1Kud3zPgYBibE2SZ/0, createdBy=da7696924, createdName=qingfengqishi5, createdTime=Thu Mar 08 07:23:43 CST 2018, time=2018-03-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=293762, encodeId=a841293e6271, content=学习了.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzTetibytbqFDmFITWHyBWbxU7S9MYibgPSqvu0sYteH0N6zXqbU0Kf3Mbdb7yWM1Kud3zPgYBibE2SZ/0, createdBy=da7696924, createdName=qingfengqishi5, createdTime=Wed Mar 07 07:17:36 CST 2018, time=2018-03-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=293470, encodeId=f5d02934e014, content=学习了.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzTetibytbqFDmFITWHyBWbxU7S9MYibgPSqvu0sYteH0N6zXqbU0Kf3Mbdb7yWM1Kud3zPgYBibE2SZ/0, createdBy=da7696924, createdName=qingfengqishi5, createdTime=Tue Mar 06 07:24:26 CST 2018, time=2018-03-06, status=1, ipAttribution=), 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2018-02-17 清风拂面

谢谢分享学习

41 0

期刊

P NATL ACAD SCI USA 进入期刊论坛 GetPortalImpactFactorByIdResponse(projectId=1, id=db515332, cover=https://img.medsci.cn/images/journal/cover/2021/NAz_202109271316251010.jpg, fullname=PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, abbr=P NATL ACAD SCI USA, pyear=1915, frequence=Weekly, articleNumbers=71052, citedSelf2015=2.9, acceptanceRate=21.0, submissionToAcceptance=2.89, averageReviewTime=平均2.89月, reviewFee=null, pageFee=null, publishedRatio=2023年中国人文章占该期刊总数量暂无数据 (2022年为100.00%), issn=0027-8424, greenSci=https://www.greensci.net/search?kw=0027-8424, scijournal=https://www.scijournal.org/impact-factor-of-P-NATL-ACAD-SCI-USA.shtml, medsciHotlightString=null, medsciHotlightRealtime=15.265, medsciHotlight=25.894, medsciHotlight5year=35.4281, citescore=19.0, hIndex=771, impactFactor=11.1, orgnization=National Academy of Sciences, orgnizationUrl=http://www.nasonline.org/site/, country=United States, countryCn=美国, isOa=0, isOaString=否, sciScie=Science Citation Index|Science Citation Index Expanded|Current Contents - Agriculture, Biology & Environmental Sciences|Current Contents - Life Sciences|Zoological Record|BIOSIS Previews, bigclassCas=综合性期刊 1区[Top], smallclassCas=综合性期刊 1 区, website=http://www.pnas.org/, websiteHits=42021, guideForAuthor=null, guideForAuthorHits=52, submitWebsite=https://www.pnascentral.org/cgi-bin/main.plex|https://www.pnascentral.org/cgi-bin/main.plex, submitWebsiteHits=13337, content=PNAS is one of the world's most-cited multidisciplinary scientific serials. Since its establishment in 1915, it continues to publish cutting-edge research reports, commentaries, reviews, perspectives, colloquium papers, and actions of the Academy. Coverage in PNAS spans the biological, physical, and social sciences. PNAS is published biweekly in print, and weekly online in PNAS Early Edition., totalCites=788686, brief=P NATL ACAD SCI USA杂志综合性期刊行业，“<a target="_blank" href="/sci/index.do?smallclass=综合性期刊" >综合性期刊</a>”子行业的顶级杂志, articleType=绝大部分收录论著，也接收少量其它类型文章, medsciHeat=暗红, medsciComment=P NATL ACAD SCI USA 在该细分领域可能是国际一流杂志，但是国内关注少，可能与很难投中有关吧，可以试试，但不要报过高中的期望哦。, medsciExplanation=MedSci期刊指数是根据中国科研工作者（含医学临床，基础，生物，化学等学科）对SCI杂志的认知度，熟悉程度，以及投稿的量等众多指标综合评定而成。当然，具体的，您还可以结合“<a href='//www.sandwebs.com/sci/submit.do?id=db515332'>投稿经验系统</a>”，进行综合判断，这更是大家的实战经验，值得分享和参考。 注意，上述MedSci期刊指数采用MedSci专利技术，由计算机系统自动计算，并给出建议，存在不准确的可能，仅供您投稿选择杂志时参考。, tags=[ImpactFactorTagDto(id=4027, tagName=生物学, createdHits=3), ImpactFactorTagDto(id=2005, tagName=细胞生物学, createdHits=1), ImpactFactorTagDto(id=2935, tagName=发育, createdHits=1), ImpactFactorTagDto(id=979, tagName=微生物, createdHits=1), ImpactFactorTagDto(id=27394, tagName=药理学, createdHits=1), ImpactFactorTagDto(id=41256, tagName=发育生物学, createdHits=1), ImpactFactorTagDto(id=2615, tagName=血液病, createdHits=1), ImpactFactorTagDto(id=44, tagName=医学, createdHits=1), ImpactFactorTagDto(id=51937, tagName=社会和经济学, createdHits=1), ImpactFactorTagDto(id=51935, tagName=物质科学, createdHits=1), ImpactFactorTagDto(id=10938, tagName=生物医学, createdHits=1), ImpactFactorTagDto(id=2964, tagName=分子生物学, createdHits=1), ImpactFactorTagDto(id=9605, tagName=神经生物学, createdHits=1), ImpactFactorTagDto(id=49245, tagName=有重要意义, createdHits=1), ImpactFactorTagDto(id=49244, tagName=有重大突破和发现, createdHits=1), ImpactFactorTagDto(id=6352, tagName=基础研究, createdHits=1), ImpactFactorTagDto(id=11018, tagName=生物, createdHits=1), ImpactFactorTagDto(id=42309, tagName=biochemistry, createdHits=1), ImpactFactorTagDto(id=16277, tagName=物理, createdHits=1)], citeScoreList=[GetImpactFactorCiteScoreListResponse(year=2017, citescore=8.59), GetImpactFactorCiteScoreListResponse(year=2018, citescore=8.58), GetImpactFactorCiteScoreListResponse(year=2019, citescore=15.7), GetImpactFactorCiteScoreListResponse(year=2020, citescore=16.2), GetImpactFactorCiteScoreListResponse(year=2023, citescore=19.0)], medsciIndexList=[GetImpactFactorMedsciIndexListResponse(year=2020, medsciHotlight=34.981), GetImpactFactorMedsciIndexListResponse(year=2021, medsciHotlight=36.612), GetImpactFactorMedsciIndexListResponse(year=2022, medsciHotlight=27.107), GetImpactFactorMedsciIndexListResponse(year=2023, medsciHotlight=19.983), GetImpactFactorMedsciIndexListResponse(year=2024, medsciHotlight=15.265)], citeScoreGradeList=[GetImpactFactorCiteScoreGradeResponse(smallClass=Multidisciplinary - Multidisciplinary , rank=4/90)], pmcUrl=https://www.ncbi.nlm.nih.gov/nlmcatalog?term=0027-8424[ISSN], pubmedUrl=https://www.ncbi.nlm.nih.gov/pubmed?cmd=search&term=PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA[ta], article_number=2489, article_number_cn=302, isJournalMember=null, journalType=sci)

投稿信息杂志简介 MedSci指数

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