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Blood：CD19/CD3双特异性抗体为慢性淋巴细胞白血病患者，特别是依鲁替尼耐药的患者，带来新的希望

2018-05-11 MedSci MedSci原创

CD19/CD3双特异性抗体慢性淋巴细胞白血病依鲁替尼博纳吐单抗
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Bruton酪氨酸激酶抑制剂依鲁替尼用于慢性淋巴细胞白血病（CLL）患者可获得较高的诱导缓解。但是，仍需要进行辅助治疗强化缓解，以克服耐药性。博纳吐单抗，CD19/CD3的双特异性抗体（bsAb），已获得FDA批准用于治疗复发性/难治性B细胞前体急性淋巴细胞白血病。由于博纳吐单抗半衰期短，仅2.1小时，需持续静脉点滴来保证疗效。Hannah R. Robinson等人开发了一种新型的单链的Fv-F

Bruton酪氨酸激酶抑制剂依鲁替尼用于慢性淋巴细胞白血病（CLL）患者可获得较高的诱导缓解。但是，仍需要进行辅助治疗强化缓解，以克服耐药性。博纳吐单抗，CD19/CD3的双特异性抗体（bsAb），已获得FDA批准用于治疗复发性/难治性B细胞前体急性淋巴细胞白血病。

由于博纳吐单抗半衰期短，仅2.1小时，需持续静脉点滴来保证疗效。Hannah R. Robinson等人开发了一种新型的单链的Fv-Fc形式的CD19/CD3 bsAb（CD19/CD3-scFv-Fc），半衰期长达5天。

在体外，CD19/CD3-scFv-Fc和博纳吐单抗均可诱导杀伤90%以上的CLL细胞（来源于初始治疗的患者）。抗白血病活性是通过增强自体CD8和CD4阳性T细胞增殖、活化和颗粒酶B的表达发挥。

在NOD/SCID/IL2Rγnull的患者来源的移植瘤小鼠模型上，予以CD19/CD3-scFv-Fc（1次/周）治疗，可消灭血液和脾脏中98%以上的CLL细胞。与此相对比，博纳吐单抗，即使是每日用药，依然不能诱导缓解。

此外，研究人员进一步在依鲁替尼治疗和耐药性的背景下探究CD19/CD3-scFv-Fc的活性。与直接采用CD19/CD3-scFv-Fc治疗的患者相比，采用依鲁替尼治疗的患者的CLL细胞可快速被CD19/CD3-scFv-Fc诱导杀伤。研究人员还证实CD19/CD3-scFv-Fc还具有抗携带BTK和（或）PLCG2突变的获得性依鲁替尼耐药的患者来源的CLL细胞的活性，无论是在体外还是在患者来源的移植瘤模型上。

总而言之，本研究结果支持将CD19/CD3 bsAbs和其他T细胞招募性bsAbs作为CLL的免疫疗法进行研究，特别是与依鲁替尼联合或作为依鲁替尼耐药性疾病的补救疗法。

原始出处：

Hannah R. Robinson，et al.A CD19/CD3 bispecific antibody for effective immunotherapy of chronic lymphocytic leukemia in the ibrutinib era. Blood  2018  ：blood-2018-02-830992；  doi： https：//doi.org/10.1182/blood-2018-02-830992

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    2018-05-25 mhzhuang@stu.e

    #CD19/CD3双特异性抗体#

    0

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    2019-01-01 jinweidong

    #特异性#

    0

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    2018-07-28 sunyl07

    #淋巴细胞白血病#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1782721, encodeId=ea161e8272103, content=<a href='/topic/show?id=effe4281cd' target=_blank style='color:#2F92EE;'>#CD19/CD3双特异性抗体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4281, encryptionId=effe4281cd, topicName=CD19/CD3双特异性抗体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=416347, createdName=mhzhuang@stu.e, createdTime=Fri May 25 15:31:00 CST 2018, time=2018-05-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1899218, encodeId=edee189921845, content=<a href='/topic/show?id=6f746e94170' target=_blank style='color:#2F92EE;'>#特异性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67941, encryptionId=6f746e94170, topicName=特异性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dc7a157, createdName=jinweidong, createdTime=Tue Jan 01 04:31:00 CST 2019, time=2019-01-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1997898, encodeId=7559199e89813, content=<a href='/topic/show?id=75ff66001cd' target=_blank style='color:#2F92EE;'>#淋巴细胞白血病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66001, encryptionId=75ff66001cd, topicName=淋巴细胞白血病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1be8234, createdName=sunyl07, createdTime=Sat Jul 28 16:31:00 CST 2018, time=2018-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302165, encodeId=6ec3130216542, content=<a href='/topic/show?id=82a6659902c' target=_blank style='color:#2F92EE;'>#淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65990, encryptionId=82a6659902c, topicName=淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e34303, createdName=wetgdt, createdTime=Sun May 13 00:31:00 CST 2018, time=2018-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1416434, encodeId=31eb14164340d, content=<a href='/topic/show?id=924442e98f' target=_blank style='color:#2F92EE;'>#CD19#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4279, encryptionId=924442e98f, topicName=CD19)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f1583186918, createdName=dingxiaobo, createdTime=Sun May 13 00:31:00 CST 2018, time=2018-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1526440, encodeId=205e152644097, content=<a href='/topic/show?id=1e416e954c3' target=_blank style='color:#2F92EE;'>#特异性抗体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67954, encryptionId=1e416e954c3, topicName=特异性抗体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b8b711724149, createdName=hyf032, createdTime=Sun May 13 00:31:00 CST 2018, time=2018-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314094, encodeId=5bcf314094a6, content=了解了解.学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Fri May 11 09:38:28 CST 2018, time=2018-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314092, encodeId=264e3140922a, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfBfgWn9nXBgH1sNSiaOAKhsKpN40jDHQKqcRzovau5VibLvREN8uxnu9sKoScBicHSiaDMmbveibFdrBiaD4k4IOPwlG/0, createdBy=b5d11730951, createdName=Jackie Li, createdTime=Fri May 11 09:37:24 CST 2018, time=2018-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314091, encodeId=85e7314091d2, content=很好的学习机会, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/04/12/cd30eefc465f70dc4dad89bd57479781.jpg, createdBy=02be2318568, createdName=一天没事干, createdTime=Fri May 11 09:37:03 CST 2018, time=2018-05-11, status=1, ipAttribution=)]
    2018-05-13 wetgdt

    #淋巴细胞#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1782721, encodeId=ea161e8272103, content=<a href='/topic/show?id=effe4281cd' target=_blank style='color:#2F92EE;'>#CD19/CD3双特异性抗体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4281, encryptionId=effe4281cd, topicName=CD19/CD3双特异性抗体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=416347, createdName=mhzhuang@stu.e, createdTime=Fri May 25 15:31:00 CST 2018, time=2018-05-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1899218, encodeId=edee189921845, content=<a href='/topic/show?id=6f746e94170' target=_blank style='color:#2F92EE;'>#特异性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67941, encryptionId=6f746e94170, topicName=特异性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=dc7a157, createdName=jinweidong, createdTime=Tue Jan 01 04:31:00 CST 2019, time=2019-01-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1997898, encodeId=7559199e89813, content=<a href='/topic/show?id=75ff66001cd' target=_blank style='color:#2F92EE;'>#淋巴细胞白血病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66001, encryptionId=75ff66001cd, topicName=淋巴细胞白血病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1be8234, createdName=sunyl07, createdTime=Sat Jul 28 16:31:00 CST 2018, time=2018-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302165, encodeId=6ec3130216542, content=<a href='/topic/show?id=82a6659902c' target=_blank style='color:#2F92EE;'>#淋巴细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65990, encryptionId=82a6659902c, topicName=淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e34303, createdName=wetgdt, createdTime=Sun May 13 00:31:00 CST 2018, time=2018-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1416434, encodeId=31eb14164340d, content=<a href='/topic/show?id=924442e98f' target=_blank style='color:#2F92EE;'>#CD19#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4279, encryptionId=924442e98f, topicName=CD19)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f1583186918, createdName=dingxiaobo, createdTime=Sun May 13 00:31:00 CST 2018, time=2018-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1526440, encodeId=205e152644097, content=<a href='/topic/show?id=1e416e954c3' target=_blank style='color:#2F92EE;'>#特异性抗体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67954, encryptionId=1e416e954c3, topicName=特异性抗体)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b8b711724149, createdName=hyf032, createdTime=Sun May 13 00:31:00 CST 2018, time=2018-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314094, encodeId=5bcf314094a6, content=了解了解.学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Fri May 11 09:38:28 CST 2018, time=2018-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314092, encodeId=264e3140922a, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfBfgWn9nXBgH1sNSiaOAKhsKpN40jDHQKqcRzovau5VibLvREN8uxnu9sKoScBicHSiaDMmbveibFdrBiaD4k4IOPwlG/0, createdBy=b5d11730951, createdName=Jackie Li, createdTime=Fri May 11 09:37:24 CST 2018, time=2018-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314091, encodeId=85e7314091d2, content=很好的学习机会, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/04/12/cd30eefc465f70dc4dad89bd57479781.jpg, createdBy=02be2318568, createdName=一天没事干, createdTime=Fri May 11 09:37:03 CST 2018, time=2018-05-11, status=1, ipAttribution=)]
    2018-05-13 dingxiaobo

    #CD19#

    0

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    2018-05-13 hyf032

    #特异性抗体#

    0

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    2018-05-11 1dd8c52fm63(暂无匿称)

    了解了解.学习学习

    0

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    2018-05-11 Jackie Li

    学习

    0

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    2018-05-11 一天没事干

    很好的学习机会

    0

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