STM:提高实体瘤治疗效果,中国药科大学张灿团队开发出T细胞表面锚定技术

2020-11-30 Bio生物世界 Bio生物世界

过继性T细胞疗法虽然在血液瘤治疗中已取得优异的治疗效果,但治疗实体瘤仍面临巨大挑战。虽然目前已有将过继T细胞与细胞因子或免疫检查点抑制剂联用以改善实体瘤的治疗,但仍面临严重不良反应及系统性毒性等局限。

过继性T细胞疗法虽然在血液瘤治疗中已取得优异的治疗效果,但治疗实体瘤仍面临巨大挑战。虽然目前已有将过继T细胞与细胞因子或免疫检查点抑制剂联用以改善实体瘤的治疗,但仍面临严重不良反应及系统性毒性等局限。而脂质代谢调节或许是一种更为安全有效的改善T细胞活力的策略。

2020年11月25日,中国药科大学药物科学研究院张灿教授团队在 Science 子刊 Science Translational Medicine 杂志发表了题为:Combination of Metabolic Intervention and T Cell Therapy via Cell-Surface Anchor-Engineering Augments Solid Tumor Immunotherapy 的研究论文。

研究团队提出将脂质代谢调节药物阿伐麦布(Avasimibe)与过继T细胞用于实体瘤联合治疗的新策略。利用T细胞表面锚定工程化技术实现代谢调节与过继T细胞疗法协同治疗实体瘤的目的。

该团队建立了新型的T细胞表面锚定技术,即模拟跨膜蛋白的特性,利用疏水作用力先将脂质锚定在T细胞膜上,再将脂质与药物脂质体通过点击反应偶联在T细胞膜上。这种细胞表面锚定技术具有不影响膜蛋白的功能、不干预T细胞的正常生理功能、温和快速等优势,并可以用于其他细胞的表面工程化改造。

新型工程化T细胞(图1)中的阿伐麦布通过“自分泌和旁分泌”的双重作用增加T细胞膜上的胆固醇水平,促进T细胞受体(T cell receptor,TCR)的快速聚集以及增加T细胞的持久活力,从而提高过继T细胞对实体瘤的治疗效果。

图1.新型表面锚定工程化T细胞用于实体瘤治疗的示意图

研究表明,新型鼠源工程化TCR-T(T cell receptor-gene engineered T cells)和人工程化CAR-T(Chimetic antigen receptor T cells)分别在原位黑色素瘤、肺转移黑色素瘤及原位胶质母细胞瘤小鼠模型中展示出优异的治疗效果。其中,工程化CAR-T细胞在原位胶质母细胞瘤小鼠模型中的完全缓解率达到60%,且生存期延长至100天以上。并且这种联用策略具有较好的体内安全性。该研究为过继T细胞用于实体瘤治疗提供了新策略,也为细胞工程化改造提供了新技术。

博士后郝玫茜和侯思源为本文共同第一作者,张灿教授、鞠曹云副研究员为本文共同通讯作者。

原始出处:

Meixi Hao,Siyuan Hou,Weishuo Li,et al.Combination of metabolic intervention and T cell therapy enhances solid tumor immunotherapy.Science Translational Medicine. 25 Nov 2020:Vol. 12, Issue 571, eaaz6667DOI: 10.1126/scitranslmed.aaz6667

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    2021-09-08 gdsun
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    2020-12-28 chenailuoding

    厉害

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1649748, encodeId=90861649e48a2, content=<a href='/topic/show?id=4a8b220090b' target=_blank style='color:#2F92EE;'>#中国药科大学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22009, encryptionId=4a8b220090b, topicName=中国药科大学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e4823916450, createdName=yzh407, createdTime=Sat Jan 09 10:43:20 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1894191, encodeId=fdf118941913f, content=<a href='/topic/show?id=5e456463eee' target=_blank style='color:#2F92EE;'>#治疗效果#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64637, encryptionId=5e456463eee, topicName=治疗效果)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=373a131, createdName=jxrzshh, createdTime=Wed Jul 21 02:43:20 CST 2021, time=2021-07-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1678011, encodeId=f54216e8011a2, content=<a href='/topic/show?id=29a8168130f' target=_blank style='color:#2F92EE;'>#STM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16813, encryptionId=29a8168130f, topicName=STM)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d76127619556, createdName=gdsun, createdTime=Wed Sep 08 07:43:20 CST 2021, time=2021-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=911777, encodeId=d978911e77ab, content=厉害, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/fXTpaKzseoS4jkHvAFv4DKtp4WxxW3BICYKTGmQom1R7cb9YiaLoVhsOFZzqOILRic6KOzpCANrxylI14QylpSnQ/132, createdBy=e5c95236994, createdName=chenailuoding, createdTime=Mon Dec 28 23:54:24 CST 2020, time=2020-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032719, encodeId=644f1032e194d, 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=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Mon Nov 30 14:43:20 CST 2020, time=2020-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1047229, encodeId=6835104e22997, content=疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Mon Nov 30 14:43:20 CST 2020, time=2020-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=903541, encodeId=d810903541ea, content=提高实体瘤治疗效果, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2020/02/20/44e485222679b3a7b0d5676ca7443126.jpg, createdBy=ef735089224, createdName=随风1991, createdTime=Mon Nov 30 13:35:31 CST 2020, time=2020-11-30, status=1, ipAttribution=)]
    2020-11-30 内科新手

    谢谢梅斯提供这么好的信息,学到很多

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1649748, encodeId=90861649e48a2, content=<a href='/topic/show?id=4a8b220090b' target=_blank style='color:#2F92EE;'>#中国药科大学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22009, encryptionId=4a8b220090b, topicName=中国药科大学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e4823916450, createdName=yzh407, createdTime=Sat Jan 09 10:43:20 CST 2021, time=2021-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1894191, encodeId=fdf118941913f, content=<a href='/topic/show?id=5e456463eee' target=_blank style='color:#2F92EE;'>#治疗效果#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64637, encryptionId=5e456463eee, topicName=治疗效果)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=373a131, createdName=jxrzshh, createdTime=Wed Jul 21 02:43:20 CST 2021, time=2021-07-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1678011, encodeId=f54216e8011a2, content=<a href='/topic/show?id=29a8168130f' target=_blank style='color:#2F92EE;'>#STM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16813, encryptionId=29a8168130f, topicName=STM)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d76127619556, createdName=gdsun, createdTime=Wed Sep 08 07:43:20 CST 2021, time=2021-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=911777, encodeId=d978911e77ab, content=厉害, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/fXTpaKzseoS4jkHvAFv4DKtp4WxxW3BICYKTGmQom1R7cb9YiaLoVhsOFZzqOILRic6KOzpCANrxylI14QylpSnQ/132, createdBy=e5c95236994, createdName=chenailuoding, createdTime=Mon Dec 28 23:54:24 CST 2020, time=2020-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032719, encodeId=644f1032e194d, 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=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Mon Nov 30 14:43:20 CST 2020, time=2020-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1047229, encodeId=6835104e22997, content=疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Mon Nov 30 14:43:20 CST 2020, time=2020-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=903541, encodeId=d810903541ea, content=提高实体瘤治疗效果, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2020/02/20/44e485222679b3a7b0d5676ca7443126.jpg, createdBy=ef735089224, createdName=随风1991, createdTime=Mon Nov 30 13:35:31 CST 2020, time=2020-11-30, status=1, ipAttribution=)]
    2020-11-30 CHANGE

    疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的

    0

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    2020-11-30 随风1991

    提高实体瘤治疗效果

    0

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