Blood:SLAMF7-CAR T细胞可清除骨髓瘤细胞,

2017-11-01 qinqiyun MedSci原创

SLAMF7正作为免疫治疗多发性骨髓瘤的靶点被进行大量研究。Tea Gogishvili等人通过huLuc63抗体(Elotuzumab)诱导嵌合抗原受体(CAR)表达,来重置T细胞对SLAMF7的特异性,并且证明了无论是来源于患者的还是健康捐献者的SLAMF7-CAR T细胞均获得抗骨髓瘤活性。

中心点:

SLAMF7-CAR T细胞是一种治疗蛋白酶抑制剂/IMiD-难治性骨髓瘤的有效疗法。

SLAMF7-CAR T细胞选择性杀伤SLAMF7高表达的正常淋巴细胞。

摘要:

SLAMF7正作为免疫治疗多发性骨髓瘤的靶点被进行大量研究。Tea Gogishvili等人通过huLuc63抗体(Elotuzumab)诱导嵌合抗原受体(CAR)表达,来重置T细胞对SLAMF7的特异性,并且证明了无论是来源于患者的还是健康捐献者的SLAMF7-CAR T细胞均获得抗骨髓瘤活性。

研究人员还证实在未进行过治疗的患者和接受过蛋白酶体抑制剂和免疫调节剂(IMiDs)治疗的复发性/难治性(R/R)患者的恶性浆细胞上,SLAMF7表达水平高且统一。

在体外,SLAMF7-CAR T细胞可促使既往未治疗过的和R/R原发性骨髓瘤细胞快速溶解。除此之外,SLAMF7-CAR T细胞的单一管理可用于分辨小鼠移植瘤模型体内髓内和髓外的骨髓瘤。部分正常的淋巴细胞可表达SLAMF7,包括NK细胞、T细胞和B细胞。

通过SLAMF7-CAR修饰,CD8+和CD4+T细胞也可迅速获得并维持SLAMF7表型,并且可迅速扩展到治疗相关的细胞剂量。Tea Gogishvili等人对SLAMF7-CAR T细胞如何识别正常的淋巴细胞进行分析发现其诱导SLAMF7+/high NK细胞, CD4+和CD8+T细胞和B细胞选择性杀伤。重要的是,SLAMF7-CAR T细胞所诱导的细胞杀伤可保留每个细胞集的SLAMF7-/low的部分,并保护功能性淋巴细胞,包括病毒特异性T细胞。

总之,Tea Gogishvili等人的研究数据表明利用SLAMF7-CAR T细胞疗法治疗多发性骨髓瘤,是一种潜在的有效疗法,并为后续研究SLAMF7提供一种新的视角。

原始出处:

Tea Gogishvili,et al.SLAMF7-CAR T-cells eliminate myeloma and confer selective fratricide of SLAMF7+ normal lymphocytes.Blood  2017  :blood-2017-04-778423;  doi: https://doi.org/10.1182/blood-2017-04-778423

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    2018-05-07 lxg951
  2. 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    2017-11-03 斯嘉莉
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    2017-11-02 半夏微凉

    学习了谢谢分享

    0

  4. 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    2017-11-02 Evangelin

    惰性多发性骨髓瘤现在的进展怎样?

    0

  5. 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    2017-11-02 明月清辉

    谢谢分享.学习了

    0

  6. 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    2017-11-02 yfjms

    学习了

    0

  7. 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authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Thu Nov 02 00:46:17 CST 2017, time=2017-11-02, status=1, ipAttribution=)]
    2017-11-02 yfjms

    学习了

    0

  8. 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topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Thu Nov 02 07:07:00 CST 2017, time=2017-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=257971, encodeId=8d0725e971a7, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3da1990174, createdName=yfjms, createdTime=Thu Nov 02 07:06:43 CST 2017, time=2017-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=257957, encodeId=4cce25e957cd, content=谢谢分享.阅读, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, 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authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Thu Nov 02 00:46:17 CST 2017, time=2017-11-02, status=1, ipAttribution=)]
    2017-11-02 刘煜

    谢谢分享.阅读

    0

  9. 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    2017-11-02 yjs木玉

    好好好好好好好好

    0

  10. 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    2017-11-02 jihuaijun1112

    学习学习学习

    0

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多发性骨髓瘤疾病进展和复发的主要原因是多发性骨髓瘤浆细胞重新进入循环系统以及在骨髓中进行播散。骨髓缺氧增加与多发性骨髓瘤浆细胞再循环增加有关。CANCER RES近期发表了一篇文章,研究在慢性缺氧过程中,HIF-2α活化是否可以克服基质分泌CXCL12提供的骨髓抑制信号,从而促进多发性骨髓瘤浆细胞播散。

NCCN临床实践指南:多发性骨髓瘤(2018.V2)

2017年10月,美国国家综合癌症网络(NCCN)发布了多发性骨髓瘤实践指南2018年第2版,指南主要内容涉及: 指南更新摘要 多发性骨髓瘤最初诊断和临床表现 孤立性浆细胞瘤初级治疗 多发性骨髓瘤初级治疗和随访/监测 活动性骨髓瘤随访/监测 干细胞移植术后治疗 活动性疾病:复发或进展性疾病的附加治疗 多发性骨髓瘤的定义 分期 多发性骨髓瘤的反应标准 骨髓瘤的治疗 辅助治疗

Blood:嵌合抗原受体(CARs)为多发性骨髓瘤带来新的治疗前景。

现在为止,多发性骨髓瘤(MM)几乎是一种不可治愈的浆细胞(B细胞)恶性肿瘤,因此探索新的治疗方式迫在眉睫。T细胞疗法是一种新的有望治愈MM的方法,其作用机制与现有的MM的标准疗法不同。

Blood:Ixazomib显着延长复发性/难治性骨髓瘤患者的无进展生存期。

多发性骨髓瘤(MM)患者的显着特点是携带某些细胞遗传学异常。现3期TOURMALINE-MM1研究证明Ixazomib+来那度胺+地塞米松(IRd)的联合疗法比来那度胺+地塞米松(Rd)可显着延长患者无进展生存期(PFS)。