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J Clin Invest：试金石！成像活化T细胞可快速判断癌症免疫疗法的疗效

2018-05-16 M记 生物探索

成像活化T细胞快速判断癌症免疫疗法疗效
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癌症疫苗是癌症免疫治疗的一个热门方向，其在根除局部和扩散恶性肿瘤方面具有很大的潜能。遗憾的是，癌症疫苗成效却不理想。现在，来自于斯坦福大学医学院的科学家们找到了一种快速判断癌症免疫疗法是否有效的方法——针对激活的T细胞进行非侵入性成像！

癌症疫苗是癌症免疫治疗的一个热门方向，其在根除局部和扩散恶性肿瘤方面具有很大的潜能。遗憾的是，癌症疫苗成效却不理想。现在，来自于斯坦福大学医学院的科学家们找到了一种快速判断癌症免疫疗法是否有效的方法——针对激活的T细胞进行非侵入性成像！

PET显像是一种可在活体上显示生物分子代谢、受体及神经介质活动的新型影像技术，，有望实现无创、实时的动态免疫反应可视化。在最新的研究中，研究团队开发了一组小分子代谢PET示踪剂，适用于免疫细胞成像。

“仅仅对所有的T细胞成像是不够的，我们需要对激活的T细胞进行成像，因为这些细胞是用来杀死肿瘤的，”斯坦福大学放射学Sanjiv Gambhir教授说，“之前的方法不够灵敏，它们在肿瘤组中检测到的T细胞并不总是激活状态的（负责消灭肿瘤细胞）。所以我们需要一种追踪激活T细胞的特异性方法。”

在最新的研究中，Sanjiv Gambhir团队掌握了这一“追踪器”，有望评估癌症疫苗的有效性。除了癌症，Gambhir认为PET示踪剂还适用于自身免疫性疾病，因为它可以附着在标记任何活化T细胞的分子上。

研究结果于5月14日以“Imaging activated T cells predicts response to cancer vaccines”为题发表在《journal of clinical investigation》杂志上。

1研究思路

示踪剂诞生于与肿瘤学教授Ronald Levy博士的合作中，后者正在研发最具前景的癌症疫苗。不同于传统的预防性注射，癌症疫苗促使T细胞进入活化状态，并使其攻击体内的肿瘤。但是，癌症疗法并不是一剂通用的（one-dose-fits-all），所以关键的问题变成：如何知道疫苗是否正在工作？

Gambhir说：“我们的挑战是，要找到一种几乎只存在于活化T细胞上的分子。”巧合的是，他发现的这个分子和他在疫苗中靶向的一种叫做OX40的激活T细胞表面的蛋白质是一样的。

结果，他们选择了激活性受体OX40，位于T细胞表面。针对OX40，他们开发了示踪剂——它会扫描整个身体（包括免疫系统），一旦识别到OX40并与之结合，放射性复合物在PET扫描下发光，从而显示出体内已成功活化的T细胞。如果未能检测到T细胞信号，则意味着医生应该重新评估免疫疗法剂量或完全改变治疗过程。

2研究结果

Gambhir的实验室首先在细胞培养中测试了示踪剂。他们发现，这种化合物能够发现95%活化的T细胞。随后，在一组约50只的小鼠模型中，PET示踪剂同样能精确地找到90%的活化T细胞。

Gambhir说：“PET扫描通常只关注肿瘤细胞。但是现在，用这种新的成像剂，我们能够对免疫细胞进行成像。”

通常，医生可以等待肿瘤体积的物理变化，以确定治疗是否有效，但是这可能需要数周甚至数月，在这期间，癌症依然会恶化。所以很明显，尽快了解病情进展，可以为病人争取更多的时间尝试其他选择。

3临床试验

Levy已经开始癌症疫苗的临床I期试验。在接下来的几个月中，Gambhir计划将这个新的OX40示踪剂应用到同一临床试验中，以便对示踪剂和癌症疫苗进行联合测试。

Gambhir表示：“从免疫疗法开始的48小时内，我们就能预测哪只小鼠对免疫疗法做出反应。”

原始出处：
Alam IS, Mayer AT, Sagiv-Barfi,et al. Imaging activated T cells predicts response to cancer vaccines.J Clin Invest. 2018 May 14. pii: 98509. doi: 10.1172/JCI98509. [Epub ahead of print]

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    2018-12-22 xiangyuzhou971

    #EST#

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  2. [GetPortalCommentsPageByObjectIdResponse(id=2051147, encodeId=05bc205114e38, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Sat Dec 22 04:23:00 CST 2018, time=2018-12-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319496, encodeId=d18a31949666, content=学习了.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Tue May 29 00:17:19 CST 2018, time=2018-05-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319174, encodeId=18a03191e4f4, content=好文章.学习了., beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Mon May 28 00:15:06 CST 2018, time=2018-05-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=317653, encodeId=579431e65337, content=学习了.好文章., beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Wed May 23 00:09:43 CST 2018, time=2018-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1031763, encodeId=6e6f1031e6373, content=谢谢梅斯提供这么好的信息，学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Wed May 16 13:23:00 CST 2018, time=2018-05-16, status=1, ipAttribution=)]
    2018-05-29 1e0f8808m18(暂无匿称)

    学习了.谢谢分享!

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  3. [GetPortalCommentsPageByObjectIdResponse(id=2051147, encodeId=05bc205114e38, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Sat Dec 22 04:23:00 CST 2018, time=2018-12-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319496, encodeId=d18a31949666, content=学习了.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Tue May 29 00:17:19 CST 2018, time=2018-05-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319174, encodeId=18a03191e4f4, content=好文章.学习了., beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Mon May 28 00:15:06 CST 2018, time=2018-05-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=317653, encodeId=579431e65337, content=学习了.好文章., beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Wed May 23 00:09:43 CST 2018, time=2018-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1031763, encodeId=6e6f1031e6373, content=谢谢梅斯提供这么好的信息，学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Wed May 16 13:23:00 CST 2018, time=2018-05-16, status=1, ipAttribution=)]
    2018-05-28 1e0f8808m18(暂无匿称)

    好文章.学习了.

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  4. [GetPortalCommentsPageByObjectIdResponse(id=2051147, encodeId=05bc205114e38, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Sat Dec 22 04:23:00 CST 2018, time=2018-12-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319496, encodeId=d18a31949666, content=学习了.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Tue May 29 00:17:19 CST 2018, time=2018-05-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319174, encodeId=18a03191e4f4, content=好文章.学习了., beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Mon May 28 00:15:06 CST 2018, time=2018-05-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=317653, encodeId=579431e65337, content=学习了.好文章., beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Wed May 23 00:09:43 CST 2018, time=2018-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1031763, encodeId=6e6f1031e6373, content=谢谢梅斯提供这么好的信息，学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Wed May 16 13:23:00 CST 2018, time=2018-05-16, status=1, ipAttribution=)]
    2018-05-23 1e0f8808m18(暂无匿称)

    学习了.好文章.

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  5. [GetPortalCommentsPageByObjectIdResponse(id=2051147, encodeId=05bc205114e38, content=<a href='/topic/show?id=95f8e042dd' target=_blank style='color:#2F92EE;'>#EST#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7042, encryptionId=95f8e042dd, topicName=EST)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9a6357, createdName=xiangyuzhou971, createdTime=Sat Dec 22 04:23:00 CST 2018, time=2018-12-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319496, encodeId=d18a31949666, content=学习了.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Tue May 29 00:17:19 CST 2018, time=2018-05-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319174, encodeId=18a03191e4f4, content=好文章.学习了., beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Mon May 28 00:15:06 CST 2018, time=2018-05-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=317653, encodeId=579431e65337, content=学习了.好文章., beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Wed May 23 00:09:43 CST 2018, time=2018-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1031763, encodeId=6e6f1031e6373, content=谢谢梅斯提供这么好的信息，学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Wed May 16 13:23:00 CST 2018, time=2018-05-16, status=1, ipAttribution=)]
    2018-05-16 内科新手

    谢谢梅斯提供这么好的信息，学到很多

    0