Blood:双特异性CD38,有望治愈多发性骨髓瘤和非霍奇金淋巴瘤!

2017-11-21 MedSci MedSci原创

已明确预定位放射免疫疗法(PRIT)在靶向肿瘤抗原时有显著的疗效,但免疫原性和内源性生物素封闭或可限制其临床转化应用。研究人员提出一种新的PRIT疗法,用于治疗多发性骨髓瘤(MM)和其他类型的B细胞恶性肿瘤,为此,研究人员开放一种抗-CD38的双特异性融合蛋白,可消除内源性生物素的干扰和免疫原性。在鼠科MM和非霍奇金淋巴瘤(NHL)的移植瘤模型上,双特异性CD38表现出良好的血液清除和肿瘤靶向的能

已明确预定位放射免疫疗法(PRIT)在靶向肿瘤抗原时有显著的疗效,但免疫原性和内源性生物素封闭或可限制其临床转化应用。

研究人员提出一种新的PRIT疗法,用于治疗多发性骨髓瘤(MM)和其他类型的B细胞恶性肿瘤,为此,研究人员开放一种抗-CD38的双特异性融合蛋白,可消除内源性生物素的干扰和免疫原性。

在鼠科MM和非霍奇金淋巴瘤(NHL)的移植瘤模型上,双特异性CD38表现出良好的血液清除和肿瘤靶向的能力。剂量检测结果显示每注射一剂量的钛-90,肿瘤吸收剂量为43.8Gy,与正常器官肝、肾、肺的吸收剂量比分别为7:1、15:1、15:1。

MM和NHL的移植瘤小鼠模型,用双特异性CD38 PRIT治疗12天,可达到100%的完全缓解(CR),最终可治愈80%的小鼠。直接对比证明双特异性 CD38的有效性等于或优于以链霉素(SA)为基础的CD38-SA PRIT疗法。每一种方法,在采取最大放疗剂量(1200uCi)时,均至少治愈75%的小鼠,而放疗剂量在600和1000uCi时,双特异性疗法则优于SA疗法,总体上多治愈35%的小鼠(p<0.004)。

双特异性PRIT的高效性,加上其可降低免疫原性和内源性生物素的干扰的风险,使双特异性CD38疗法成为有吸引力的潜在选择。考虑到难治性疾病常保持辐射敏感性。CD38 PRIT或许可使对现有疗法无反应、合并高危疾病的患者受益。研究人员认为,PRIT或许不仅是延长存活期,而是有可能治愈多发性骨髓瘤和难治性的非霍奇金淋巴瘤患者。

原始出处:

Damian J.Green,et al.CD38 bispecific antibody pretargeted radioimmunotherapy for multiple myeloma and other B cell malignancies.Blood 2017  :blood-2017-09-807610;  doi: https://doi.org/10.1182/blood-2017-09-807610

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    2018-10-21 jml2009
  2. [GetPortalCommentsPageByObjectIdResponse(id=1889819, encodeId=dc6c18898196b, content=<a href='/topic/show?id=760c430895a' target=_blank style='color:#2F92EE;'>#多发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43089, encryptionId=760c430895a, topicName=多发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04d6114, createdName=jml2009, createdTime=Sun Oct 21 15:38:00 CST 2018, time=2018-10-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=288129, encodeId=80b0288129e3, content=学习了.谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Thu Feb 15 09:08:46 CST 2018, time=2018-02-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1899173, encodeId=e5a818991e37a, 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=22, 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=Fri Sep 28 04:38:00 CST 2018, time=2018-09-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=263910, encodeId=9e9c263910d0, content=学习了谢谢分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Fri Nov 24 09:49:10 CST 2017, time=2017-11-24, status=1, ipAttribution=)]
    2018-02-15 1e145228m78(暂无匿称)

    学习了.谢谢作者分享!

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    2017-11-24 大爰

    学习了谢谢分享!!

    0