双特异性抗体:过去,现在与未来

2020-04-18 MedSci MedSci原创

双特异性抗体:过去,现在与未来,是目前最为全面的介绍与综述,包括机制,工艺,平台,挑战,用途

1960年,纽约罗斯威尔公园纪念研究所的Nisonoff及其合作者首次提出了双特异性抗体(bispecific antibodys)的原始概念。之后,随着抗体工程和抗体生物学领域的里程碑进展,构建双特异性抗体的概念和技术不断创新(图1),导致了今天所看到的100多种双特异性抗体建造模式(formats),其中,约四分之一已发展成技术平台,并由生物技术公司和制药公司商业化,用于生产新型疗法。 1961年发表了首个关于双抗产生的研究,描述了从两种单特异性抗体的混合物生产同时含有两种不同抗原结合位的嵌合双抗。此双抗同时沉淀两种对初始抗体特异的抗原。1983-2007年,IgG4分子被发展可与HL片段随机交换,这种转译后的修饰产生了嵌合双特异性分子。2012-2016,全部4个亚种双特异性IgG分子被发现存在于健康供体的血液中,胎盘和乳汁(IgG和sIgA)中。 1984年,抗T淋巴细胞受体和白血病细胞系抗原的单抗用异质双功能连接子交联,并且产生的双抗吸引T淋巴细胞并刺激T细胞介导的细胞毒性。1985年,一个双特异性Fab2由抗人CD3受体的HL片段和抗H2k小鼠蛋白的HL片段构建,产生的构造

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (4)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1899373, encodeId=6f1c18993e3ec, 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=34, 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=Mon Jul 27 11:27:28 CST 2020, time=2020-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025808, encodeId=cb7210258080f, content=双特异性抗体是热点,但是也不一定都有效!, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=研发小兵, createdTime=Tue Apr 21 14:27:28 CST 2020, time=2020-04-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1526468, encodeId=17f9152646842, 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=34, 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=Mon Apr 20 05:27:28 CST 2020, time=2020-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=381865, encodeId=1beb38186564, content=好消息,好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=43a21971117, createdName=njwbhuang, createdTime=Sat Apr 18 19:34:13 CST 2020, time=2020-04-18, status=1, ipAttribution=)]
  2. [GetPortalCommentsPageByObjectIdResponse(id=1899373, encodeId=6f1c18993e3ec, 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=34, 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=Mon Jul 27 11:27:28 CST 2020, time=2020-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025808, encodeId=cb7210258080f, content=双特异性抗体是热点,但是也不一定都有效!, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=研发小兵, createdTime=Tue Apr 21 14:27:28 CST 2020, time=2020-04-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1526468, encodeId=17f9152646842, 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=34, 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=Mon Apr 20 05:27:28 CST 2020, time=2020-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=381865, encodeId=1beb38186564, content=好消息,好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=43a21971117, createdName=njwbhuang, createdTime=Sat Apr 18 19:34:13 CST 2020, time=2020-04-18, status=1, ipAttribution=)]
    2020-04-21 研发小兵

    双特异性抗体是热点,但是也不一定都有效!

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1899373, encodeId=6f1c18993e3ec, 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=34, 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=Mon Jul 27 11:27:28 CST 2020, time=2020-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025808, encodeId=cb7210258080f, content=双特异性抗体是热点,但是也不一定都有效!, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=研发小兵, createdTime=Tue Apr 21 14:27:28 CST 2020, time=2020-04-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1526468, encodeId=17f9152646842, 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=34, 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=Mon Apr 20 05:27:28 CST 2020, time=2020-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=381865, encodeId=1beb38186564, content=好消息,好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=43a21971117, createdName=njwbhuang, createdTime=Sat Apr 18 19:34:13 CST 2020, time=2020-04-18, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=1899373, encodeId=6f1c18993e3ec, 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=34, 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=Mon Jul 27 11:27:28 CST 2020, time=2020-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025808, encodeId=cb7210258080f, content=双特异性抗体是热点,但是也不一定都有效!, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=研发小兵, createdTime=Tue Apr 21 14:27:28 CST 2020, time=2020-04-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1526468, encodeId=17f9152646842, 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=34, 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=Mon Apr 20 05:27:28 CST 2020, time=2020-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=381865, encodeId=1beb38186564, content=好消息,好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=43a21971117, createdName=njwbhuang, createdTime=Sat Apr 18 19:34:13 CST 2020, time=2020-04-18, status=1, ipAttribution=)]
    2020-04-18 njwbhuang

    好消息,好文章!

    0

相关资讯

黄慧强教授:淋巴瘤治疗进展显著,双特异性抗体等免疫治疗前景广阔

淋巴瘤是血液系统中最为常见的恶性肿瘤之一,其治疗先后经历了传统化疗及免疫化疗时代。目前,以免疫检查点抑制剂(PD-1单抗),双特异性抗体及CAR-T为代表的新型治疗手段在淋巴瘤领域中正显示出极其广阔的应用价值及前景。

Glenmark双特异性抗体GBR 1342治疗多发性骨髓瘤,喜获FDA孤儿药物指定

Glenmark Pharmaceuticals宣布其双特异性药物抗体候选GBR 1342用于先前已接受过治疗的多发性骨髓瘤患者,获得美国食品和药物管理局(FDA)的孤儿药物指定。

全球双特异性抗体的靶点大总结

截至2019年3月,全球研发管线有超过90个双特异性抗体项目。其中~86%用在肿瘤患者。其中最多的还是桥接细胞法(Bridging cell),靶点选择中,通过CD3进行T细胞招募活化占据了50%以上。 双特异性抗体通过结合两个不同的靶点分子,来开启新的活性,在作用方式上主要有两种:桥接两种细胞类型(in-trans binding)和结合一个细胞上的两个分子(in-cis binding)

安进宣布两项三期双特异性抗体BLINCYTO(靶向CD3和CD19)治疗小儿复发性急性淋巴细胞白血病患者的阳性结果

Amgen宣布其双特异抗体BLINCYTO(blinatumomab)(同时靶向CD3和CD19)针对小儿复发B细胞急性淋巴细胞白血病(ALL)的全球多中心3期临床试验(20120215)的中期分析结果已达到了无事件生存的主要终点。

研究性双特异性抗体APVO210的剂量递增研究:安全可靠

Aptevo Therapeutics是一家致力于开发新型肿瘤学、自身免疫和血液学治疗药物的生物技术公司,近日宣布已完成一项研究性双特异性抗体APVO210的I期剂量递增研究(SAD试验)。

BioNTech启动其双特异性抗体DuoBody-PD-L1x4-1BB的首次人体I / IIa期试验

德国BioNTech SE生物技术公司宣布其DuoBody-PD-L1x4-1BB的I / IIa期研究正式开始。DuoBody-PD-L1x4-1BB是与Genmab A / S联合开发的双特异性抗体,正在研究用于治疗转移性或不可切除的恶性实体瘤患者。