ÍÃÔ´µ¥¿¹Ò©Î¹ýÈ¥¡¢ÏÖÔÚÓëδÀ´

¹ýÈ¥£ºÊóÔ´Ö÷µ¼µÄÔÓ½»Áöµ¥¿¹Ò©Îï

×Ô1975Ä꣬MilsteinºÍKohler³É¹¦ÈںϳöµÚÒ»ÖêÊóÔÓ½»Áöϸ°ûºó£¬µ¥¿Ë¡¿¹Ìå±ã¿ªÊ¼½øÈë´óÖÚÊÓÒ°£¬ÔÚҽѧ¼ìÑé¡¢µ°°×Ìá´¿¡¢°ÐÏòÖÎÁƺÍÏÔÏñ¼¼ÊõÖеÃÒÔÓ¦Óá£1986Ä꣬µÚÒ»¿îµ¥¿Ë¡¿¹ÌåÒ©Orthoclone OKT3¾­FDAÉóÅúͨ¹ýºóÉÏÊУ¬¸ÃÒ©Îï°ÐÏòÈËCD3£¬ÓÃÒÔ·ÀÖ¹ÉöÔàÒÆÖ²ºóµÄËÞÖ÷ÅųâÎÊÌâ¡£Orthoclone OKT3Ò²³ÉΪÁË×îÔçµÄµÚÒ»´úÊóÔ´µ¥¿¹Ò©Îï¡£

¾­¹ý47ÄêµÄÑо¿Óë·¢Õ¹£¬Èç½ñÒÑÓÐÉÏ°ÙÖÖµ¥¿¹Ò©Îïͨ¹ýFDAÉóÅúÉÏÊУ¬Õë¶Ô°üÀ¨Ö×Áö¡¢×ÔÃâÒß²¡¡¢´«È¾²¡µÈ²»Í¬ÀàÐͼ²²¡¡£¾¡¹Ü½ö¹ýÁËÈËÔ´»¯¸ÄÔ죬¾ø´ó¶àÊýµ¥¿¹Ò©ÎïÈÔÀ´Ô´ÓÚ¶ÔÊó½øÐÐÃâÒߺó²úÉúµÄÊóÔ´¿¹Ìå¡£ÊóÔ´µ¥¿¹ËäÈ»ÖƱ¸¼¼ÊõÏà¶Ô³ÉÊ죬·¢Õ¹ÀúÊ·Ïà¶ÔÓƾ㬵«ÓÉÓÚÊó±¾ÉíÆ¢Ôà½ÏС£¬ÃâÒßϵͳ²úÉúµÄ¿¹Ìå¶àÑùÐԽϲÌåÖÖÀà½ÏÉÙµÄÌìÈ»ÁÓÊÆ£¬²»ÉÙÆóÒµÔÚ¿ª·¢¿¹Ìåƽ̨ʱ»áÉè·¨¶ÔÊ󵥿¹½øÐиÄÁ¼£»Ò²Óв»ÉÙ¹«Ë¾×ª¶øÑз¢ÍÃÔ´µ¥¿Ë¡¿¹ÌåÒ©ÒÔÑ°ÇóÍ»ÆÆ¡£Ä¿Ç°£¬ÒÑÓÐÁ½¿îÍÃÔ´µ¥¿¹Ò©³É¹¦ÉÏÊУ¬·Ö±ðÊÇÀ´×Ôŵ»ª£¨Novartis£©µÄBeovu£¨Brolucizumab£©ºÍÀ´×ÔÁé±±£¨Lundbeck£©µÄVyepti£¨Eptinezumab£©¡£

ÏÖÔÚ£ºBeovu £¨Brolucizumab£©ÓëVyepti£¨Eptinezumab£©

ÔÚÏêϸ½éÉÜBeovuÇ°£¬ÐèÒª²¹³ä½éÉÜһЩÍõ¥¿¹¿ª·¢¼¼Êõ·¢Õ¹µÄ±³¾°ÖªÊ¶¡£ÊóÔ´ÔÓ½»Áö¼¼ÊõÊÇÀûÓÃÊó½¬Ï¸°ûÓëÊóÔ´¹ÇËèÁöϸ°ûͬԴÈÚºÏÀ´»ñµÃÊóÔ´ÔÓ½»ÁöµÄ¡£È»¶ø£¬Íý¬Ï¸°ûÓëÊóÔ´¹ÇËèÁöϸ°ûÐγɵÄÍÃ-ÊóÒìÔ´ÔÓ½»Áöϸ°û·ÖÃÚ¿¹ÌåµÄЧÂʽϵͣ¬ÇÒÒìÔ´ÔÓ½»Áö²¢²»Îȶ¨£¬¼«Ò×ÍË»¯¡£Ö±µ½1997Ä꣬ÓÉÖìΰÃñ²©Ê¿É¸Ñ¡³öÊÀ½çÉϵÚÒ»ÖêÓÃÓÚ²úÉúÎȶ¨¡¢¸ßÖÊÁ¿µÄÍÃ-Íõ¥Â¡¿¹ÌåµÄÈÚºÏϸ°ûÖê¡£¸Ãϸ°ûÖê±»ÃüÃûΪ240E-W£¬ÓÉÖìΰÃñ²©Ê¿ºÍÓà¹úÁ¼²©Ê¿½¨Á¢µÄEpitomics¹«Ë¾ÕÆÎÕʹÓøÃϸ°ûÖêÖƱ¸Íõ¥¿¹ÔÓ½»Áö£¨RabMAb^?£©µÄרÀû¡£ºóÀ´Epitomics¹«Ë¾¾­ÀúÁËÊý´Î¸Ä×éÓëÊÕ¹º£¬×îÖÕRabMAb^?µÄרÀûÂäÈëÁËAbcamÓëŵ»ªµÈ¹«Ë¾ÊÖÖС£¶ø½èÓÉÍõ¥¿¹Æ½Ì¨£¬Åµ»ª×îÖճɹ¦Ñз¢³öBeovu²¢ÉÏÊС£

ͼ1 Íÿ¹Ò©Î﷢չʷ

Beovu£¨Brolucizumab£©ÉÏÊÐÓÚ2019Ä꣬ÊÇÒ»ÖÖÈËÀàѪ¹ÜÄÚƤÉú³¤Òò×Ó£¨VEGF£©ÒÖÖƼÁµÄscFvÀàÍõ¥¿¹Ò©£¬±»FDAÅú×¼ÓÃÓÚÖÎÁÆʪÐÔÄêÁäÏà¹ØÐԻư߱äÐÔ£¨AMD£©¡£

ͼ2 Beovu£¨Brolucizumab£©

ʪÐÔÄêÁäÏà¹ØÐԻư߱äÐÔ£¬Ò²³ÆΪÉø³öÐÔ»òÐÂÉúѪ¹ÜÐÔÄêÁäÏà¹ØÐԻư߱äÐÔ£¬ÊÇÓɲ£Á§Ä¤ðàµÈÒýÆðµÄBruchĤË𺦣¬ÄÜÓÕ·¢ÂöÂçĤµÄëϸѪ¹ÜÏòÍâ²ã³¤³öÐÂÉúѪ¹Ü£¬ÒýÆðÑÏÖصÄÊÓÁ¦É¥Ê§¡£Ñª¹ÜÄÚƤÉú³¤Òò×ÓÊÇÒ»¸ö¼Ò×壬°üÀ¨VEGF-A¡¢VEGF-BµÈ¡£VEGF-A¿É´Ù½øÐÂÉúѪ¹ÜÐγɺÍʹѪ¹Üͨ͸ÐÔÔö¼Ó£¬È»¶ø¹ý¶àµÄVEGF-AÔòÊÇʪÐÔAMD²úÉúµÄÔ­ÒòÖ®Ò»¡£Brolucizumabͨ¹ý×è¶ÏVEGF-AÓëÄÚƤϸ°û±íÃæVEGFÊÜÌå½áºÏ£¬¼õÉÙÐÂÉúѪ¹Ü²¡±ä£¬°ïÖú»º½âʪÐÔAMDµÄÖ¢×´£¬´Ó¶ø¼õ»ºÊÓÁ¦Ï½µ¡£

ͼ3 Brolucizumab×è¶ÏVEGF-AÓëVEGFÊÜÌå½áºÏ

BeovuÊÇÒ»ÖÖµ¥¼ÁÁ¿Æ¿×°µÄÈÜÒº£¨ÒºÌå»ìºÏÎ£¬ÒÔ×¢É䷽ʽ¸øÒ©¡£ÓÉÓÚBrolucizumabΪ¸ß¶ÈÈËÔ´»¯Íõ¥¿¹scFv£¬Æä°ëË¥Æڽϳ¤£¬½öÐèÔÚ×î³õµÄÈý´ÎÒ©ÎïÖÎÁƱ£³ÖÿÔÂÒ»´ÎµÄƵÂÊ£¬ºóÐøÿ8ÖÁ12ÖܸøÒ©Ò»´Î¡£

ͼ4 Beovu×¢ÉäÒº

ÁíÒ»·½Ã棬Vyepti£¨Eptinezumab£©×÷ΪΨһһ¿îÅú×¼ÉÏÊеÄÈ«³¤Íõ¥¿¹Ò©Î×îÔçÓÉAlder BioPharmaceuticals£¨¼ò³ÆAlder£©¹«Ë¾ËùÑз¢¡£2019Ä꣬Alder±»µ¤ÂóÆóÒµÁé±±ÖÆÒ©£¨Lundbeck£©ÒÔ19.5ÒÚÃÀÔªµÄ¼Û¸ñÊÕ¹º¡£2020Äê2Ô£¬Vyepti×÷ΪȫÇòÊ׿îÈ«³¤Íõ¥¿¹Ò©ÎïÉÏÊУ¬ÓÃÓÚÔ¤·ÀÐÔÖÎÁƳÉÈËÆ«Í·Í´¡£

Æ«Í·Í´ÊÇÒ»ÖÖ¿ÉÒýÆðÑÏÖز«¶¯ÐÔÌÛÍ´»ò²«¶¯¸ÐµÄÍ·Í´£¬Í¨³£ÔÚÍ·²¿µÄÒ»²à¡£Ëü³£³£°éËæ×ŶñÐÄ¡¢Å»Í£¬ÒÔ¼°¶Ô¹âÏߺÍÉùÒô¼«¶ÈÃô¸Ð¡£Æ«Í·Í´·¢×÷¿É³ÖÐøÊýСʱÖÁÊýÌ죬ÌÛÍ´³Ì¶È¿ÉÄܷdz£ÑÏÖØ£¬ÒÔÖÁÓÚÓ°ÏìÈÕ³£Éú»î¡£½µ¸ÆËØ»ùÒòÏà¹ØëÄ£¨Calcitonin gene related peptide, CGRP£©ÊÇÈËÀàÓ÷Ö×ÓÉúÎïѧ·½·¨·¢ÏֵĵÚÒ»¸ö»îÐÔ¶àëÄ¡£CGRPµÄÊÍ·Å»áÒýÆð¾Ö²¿Ñª¹ÜÀ©ÕÅ£¬¾¡¹Ü¾ßÌåµÄ»úÀíÉв»Ã÷È·£¬µ«ËüÈÔ±»ÈÏΪÔÚÆ«Í·Í´ÖÐÆð׏ؼü×÷Óá£

ͼ5 CGRPÓëÆ«Í·Í´

×Ô2018ÄêÒÔÀ´£¬ÃÀ¹úFDAÒѾ­Åú×¼ÁË6ÖÖ¿ÉÒÔ×è¶ÏCGRP»òÆäÊÜÌåµÄÒ©ÎVyepti±ãÊÇÆäÖÐÖ®Ò»¡£ÕâЩҩÎ︱×÷ÓÃÏà¶Ô½ÏС£¬¶øÇÒ¶ÔÓÚÐí¶à½ÓÊÜÆäËûÒ©ÎïÖÎÁÆÎÞÓ¦´ðµÄÈËȺÓÐЧ¡£Vyeptiͨ¹ýÓëCGRP½áºÏ£¬´Ó¶ø×è¶ÏCGRPÓëÆäÊÜÌåµÄ½áºÏ¹ý³ÌÀ´»º½âÆ«Í·Í´µÄÖ¢×´¡£ÓÉÓÚCGRP½öÓÉ37¸ö°±»ùËá×é³É£¬Ïà¶Ô½ÏС£¬Eptinezumab×÷ΪÍõ¥¿¹£¬¶ÔС·Ö×ӺͰ뿹ԭҲ»á²úÉú¸üÃ÷ÏÔµÄÃâÒß·´Ó¦¡£

ͼ6 Vyepti×÷ÓûúÖÆ

Ä¿Ç°Õë¶ÔCGRPÒÑÓÐËĿÌåÒ©ÎïÉÏÊУ¬³ýVyeptiÍ⣬·Ö±ðΪ°²½ø/ŵ»ªAimovig¡¢ÌÝÍßAjovy¡¢ÀñÀ´Emgality¡£Ïà±ÈÆäËûÈýÖÖÊóÔ´¿¹ÌåÒ©ÎVyeptiÊÇΨһһÖÖ¾²Âö¸øÒ©¼ÁÐÍ¡£ÓÃÒ©·½Ã棬Vyeptiÿ3¸öÔÂÒ»´Î¾²ÂöÊä×¢£¬AimovigºÍEmgality¾ùΪÿÔÂÒ»´ÎƤÏÂ×¢É䣬AjovyÔò¿ÉÿÔÂÒ»´Î»òÿ3¸öÔÂÒ»´ÎƤÏÂ×¢Éä¡£Vyepti¸øÒ©ÖÜÆÚÃ÷ÏԽϳ¤£¬¸üÄܼõÉÙ»¼ÕßÒÀ´ÓÐÔÎÊÌâ¡£

δÀ´£ºÐ°е㡢з½·¨¡¢ÐÂÌôÕ½

Ïà±ÈÊóÔ´µ¥¿¹£¬Íõ¥¿¹¾ß±¸ÌØÒìÐÔ¸ü¸ß£¬Ç׺ÍÁ¦¸üºÃ£¬Ê¶±ð±íλ¸ü¾«Ï¸µÈÓÅÊÆ¡£Í¬Ê±£¬Ô½À´Ô½¶àµÄСÊó¼²²¡Ä£ÐÍÒ²±»Í¶Èëµ½ÁÙ´²ÊÔÑéÖС£ÓÉÓÚÊóÔ´µ¥¿Ë¡¿¹Ì岻ʶ±ðÊóÔ´µ°°×£¬¸ü¶àµÄÍÃÔ´µ¥¿¹Ìæ´úÒ©Ò²Öð½¥½øÈëÊÓÒ°¡£ÖÖÖÖÔ­ÒòÏ£¬¸ü¶àÉúÎïÒ©Æó¿ªÊ¼´ÓÊÂÕë¶Ô¸ü¶à²»Í¬°ÐµãµÄÍõ¥¿¹Ò©ÎïÑз¢£¬Èç¹úÄÚ°ÂÈü¿µÒ©ÒµÕë¶ÔÒÈÏÙ°©Claudin 18.2µÄASKB589£¬ÜõÐÅÉúÎïÕë¶ÔÒøм²¡IL-17AµÄQX002NµÈÒÔ¼°¹úÍâApexigenÕë¶ÔCD40µÄAPX005MµÈ¡£Ëæןü¶àµÄÍõ¥¿¹Ò©Îï½øÈëÁÙ´²½×¶Î£¬ÈçºÎµÃµ½ÌØÒìÐÔÕë¶Ôае㲢Äܳɹ¦³ÉÒ©µÄÍõ¥¿Ë¡¿¹Ìå·Ö×Ó£¬Ò²½«³ÉΪÖî¶àÉúÎïÒ©ÆóÒµµÄÒ»´ó¹¥¿ËÄ¿±ê¡£

ͼ7 ²¿·Ö½øÈëÁÙ´²½×¶ÎÍõ¥¿¹Ò©ÎïÃûµ¥

Óë´Ëͬʱ£¬ÔÚÍõ¥¿¹Ò©ÎïÏȵ¼·Ö×Ó·¢Ïֽ׶Σ¬ÐÂʱ´úµÄ·½·¨Óë¼¼ÊõÒ²ÔÚ²»¶Ï¸üУ¬´Ó¶ø°ÚÍÑÍÿ¹Ò©Ñз¢ÊÜRabMAb^?רÀûµÄÓ°Ïì¡£µÚ¶þ´úµÄ¿¹Ìåչʾ¼¼Êõ¿ÉÒÔ±ÜÃâÍõ¥¿¹ÃâÒßÄÍÊܵÄÎÊÌ⣬²¢¿ÉÕë¶Ô¦ÊÐÍ¿¹Ì壬Ҳ¿ÉÓÃÓÚ¦ËÐ͵ĸßÇ׺ÍÁ¦¿¹Ìåɸѡ¡£×îеĵ¥Bϸ°û¼¼Êõͨ¹ýÖ±½Ó¶Ôµ¥¸öBϸ°ûµÄɸÑ¡£¬¿ÉÔÚ²»µ½Á½¸öÔµÄʱ¼ä£¬É¸Ñ¡³ö´óÁ¿µÄºòÑ¡Íõ¥¿¹·Ö×Ó¡£ÐÂƽ̨Óë¾É·½·¨µÄÅöײ£¬Ò²Ìṩ¸ø¸ü¶àÍõ¥¿¹Ñз¢Ò©Æó¸ü¶àÑ¡Ôñ¡£

ͼ8 SingleBÍõ¥¿¹ÖƱ¸Á÷³Ì

ÁíÒ»·½Ã棬ËäÈ»Íÿ¹µÄͬԴÐÔÏà½ÏÈ˵ÄͬԴÐÔ±ÈÊóÏà¶Ô½Ï¸ß£¨Ô¼60%~76%£©£¬²¢ÇÒ×î½üпª·¢µÄMutational Lineage-Guided£¨MLG£©ÈËÔ´»¯¼¼ÊõҲʹµÃRabMAbÈËÔ´»¯¸ü¼ÓÈÝÒ×£¬µ«ÓÉÓÚÍõ¥¿¹ÖØÁ´¿É±äÇøº¬ÓжîÍâµÄ¶þÁò¼ü£¬Íõ¥¿¹µÄÈËÔ´»¯ÈÔÈ»ÊÇÍõ¥¿¹·Ö×Ó³ÉÒ©µÄÒ»´óÌôÕ½¡£ÐÂƽ̨µÄ¿ª·¢»òÕßת»ùÒòÍõÄÅàÓý»òÐí»á³ÉΪδÀ´Ì½Ë÷µÄÖصã¡£

½áÓï

Íõ¥¿¹µÄµ®ÉúÊÇÇúÕ۵ģ¬Ïà±ÈÊ󵥿¹£¬ÎÞÂÛÊÇ·¢Õ¹ÀúÊ·»¹ÊÇÉÏÊÐÒ©ÊýÁ¿£¬¶¼Ïà½Ïʽ΢¡£µ«Íõ¥¿¹µÄ¸ßÇ׺ͣ¬¸ßÌØÒìµÈÓÅÊÆΪÉúÎïҽѧÑо¿ºÍ¿¹ÌåÒ©ÎïµÄ·¢Õ¹ÌṩÁË´óµÄ¿Õ¼ä¡£Íõ¥¿¹Ò©Ñз¢µÄµÀ·ÒÀȻʮ·ÖÂþ³¤£¬µ«»ùÓÚеÄƽ̨£¬¹¥¿ËеÄÀ§ÄÑ£¬Ò²±ØÈ»»áÖ¸ÏòÍõ¥¿¹Ò©¹âÃ÷µÄδÀ´¡£

²Î¿¼ÎÄÏ×
[1]Justus Weber, Haiyong Peng, Christoph Rader. From rabbit antibody repertoires to rabbit monoclonal antibodies. Experimental & Molecular Medicine 2017 (49)
[2]Thomas FT, Griesedieck C, Thomas J, Carver M, Whitley T, Warren R et al. Differential effects of horse ATG and rabbit ATG on T cell and T cell subset levels measured by monoclonal antibodies. Transplant Proc 1984; 16:1561-1563.
[3]Zhu L, Fang Y, Liu Z, Wang P, Wang Y, Xu H. Rabbit anti-human leukocyte polyclonal antibody inhibits xenogeneic cell-mediated immune responses. Transplant Proc 2008; 40: 2760-2763.
[4]FDA. Available at http://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm (using search term ¡®rabbit polyclonal antibodies¡¯, accessed on 3 October 2016).
[5]Reichert JM. Antibodies to watch in 2016. MAbs 2016; 8: 197-204.
[6]Weiner GJ. Building better monoclonal antibody-based therapeutics. Nat Rev Cancer 2015; 15: 361-370.

Ïà¹ØÔĶÁ

Íõ¥¿¹SingleB^?¿ìËÙ·¢ÏÖ

Ïà¹ØÔĶÁ

°éËæÕï¶ÏÍõ¥¿¹£ºÐÂʱ´ú¡¢ÐÂÑ¡Ôñ
·ÇÌØÒìÐÔ£ºÖÎÁÆÐÔ¿¹Ì忪·¢ÖеÄÄÑÌâ