鏈枃鎽樿

鍦ㄨ偪鐦ゆ不鐤椾腑灞曠幇寮哄ぇ娌荤枟娼滃姏鐨凕/span>ADC鑽墿锛屽叾澶ц妯″晢涓氬寲寰堝ぇ绋嬪害涓婃槸鍩轰簬鍋惰仈鎶€鏈殑绐佺牬锛屾洿鏅鸿兘鐨勮繛鎺ュ瓙鐪熸瀹炵幇鑽墿鐨勭簿鍑嗛噴鏀撅紝璁?/span>ADC鑽墿鐨勭枟鏁堝拰瀹夊叏鎬у緱鍒颁簡鏄捐憲鐨勬彁鍗囥€備负搴斿ADC鑽墿鏋侀珮鐨勭爺鍙戞垚鏈紝闄嶄綆澶辫触椋庨櫓锛岃〃寰佸叧閿川閲忓睘鎬э紙CQAs锛夋槸姝ょ被鑽墿鐮斿彂鐢熶骇鐨勫叧閿墍鍦ㄣ€傛湰鏂囦粙缁嶄簡椹皵鏂囧笗绾崇璐┛ADC鑽墿鐮斿彂鍏ㄨ繃绋嬬殑澶氱琛ㄥ緛鎶€鏈強鍏跺湪璇勪及缁撳悎娲绘€с€佷紭鍖栫ǔ瀹氭€у強鎺у埗棰楃矑褰㈡垚绛夐鍩熺殑鐩稿叧搴旂敤銆侟/span>

杩戝勾鏉ワ紝鎶椾綋鍋惰仈鑽墿锛圏/span>Antibody-Drug Conjugates, ADCs锛夐€愭笎鎴愪负鐢熺墿鎶€鏈鍩熺殑鏄庢槦浜у搧锛屽叾鐙壒鐨勬満鍒迭/span>鈥斺€擖span style="font-family:绛夌嚎">缁撳悎鎶椾綋鐨勯澏鍚戞€т笌楂樻瘨鎬у皬鍒嗗瓙鑽墿鐨勫己鏁堟潃浼ゅ姏锛屼负鐧岀棁娌荤枟鎻愪緵浜嗙簿鍑嗕笖楂樻晥鐨勮В鍐虫柟妗堛€傛牴鎹渶鏂版暟鎹紝鍏ㄧ悆鐧岀棁鎮ｈ€呮瘡骞存柊澧炵害2000涓囦緥锛岃€孅/span>ADC鑽墿宸插湪鑲跨槫娌荤枟涓睍鐜板嚭寮哄ぇ鐨勬不鐤楁綔鍔涖€備互Enhertu涓轰緥锛孅/span>2023骞磋鑽墿涓哄叾寮€鍙戣€呴樋鏂埄搴凤紙AstraZeneca锛夊拰绗竴涓夊叡锛圏/span>Daiichi Sankyo锛夊甫鏉ヤ簡25浜跨編鍏冪殑閿€鍞敹鍏ワ紝鎴愪负澶氫釜ADC鈥淈span style="font-family:绛夌嚎">閲嶇鐐稿脊鈥滭span style="font-family:绛夌嚎">鑽墿涔嬩竴銆侟/span>2023骞达紝鍏ㄧ悆ADC甯傚満鎬昏妯￠娆＄獊鐮寸櫨浜跨編鍏冨ぇ鍏炽€侟/span>鍦ㄤ腑鍥藉競鍦猴紝ADC棰嗗煙鍚屾牱鍙戝睍杩呯寷锛孅/span>2024骞村娆近/span>ADC浜у搧閫氳繃License-out妯″紡瀹炵幇浜嗛珮棰濅氦鏄擄紝涓鸿涓氭敞鍏ヤ簡寮哄姴鐨勫闀垮姩鍔涖€侟/span>

ADC鑽墿鐨勫礇璧峰苟闈炲伓鐒讹紝鍏舵垚鍔熷緱鐩婁簬澶氬勾鏉ョ敓鐗╂妧鏈殑杩涙鍜屽垱鏂般€傚崟鍏嬮殕鎶椾綋鐨勭爺鍙戝凡缁忔湁杩慄/span>40骞寸殑鍘嗗彶锛孅/span>ADC鎵€浣跨敤鐨勯珮姣掓€ц嵂鐗╋紙濡侟/span>DNA鍜屽井绠℃姂鍒跺墏锛変篃鏈夌潃闀挎湡鐨勭爺绌跺熀纭€銆備絾鐪熸鎺ㄥ姩ADC澶ц妯″晢涓氬寲鐨勬槸杩戝勾鏉ュ伓鑱旀妧鏈殑绐佺牬銆侟/span>

鏃╂湡鐨勮繛鎺ュ瓙锛圏/span>linker锛夋妧鏈洜鍖栧绋冲畾鎬у樊鑰屽鑷磋嵂鐗╁湪闈炵壒瀹氫綅缃噴鏀撅紝鏄捐憲缂╁皬浜嗘不鐤楃獥鍙ｃ€傛澶栵紝杩炴帴瀛愮殑瀹归噺鏈夐檺锛屼篃闄愬埗浜嗘姉浣撴墍鑳芥惡甯﹁嵂鐗╃殑鏁伴噺銆傝€岃繃鍘狐/span>10-15骞翠腑锛岄殢鐫€鏇存櫤鑳界殑杩炴帴瀛愯璁捐鍑烘潵锛岄€氳繃pH鏁忔劅鎬ф垨闈剁粏鑳炲唴鍒囧壊鏈哄埗瀹炵幇鑽墿鐨勭簿鍑嗛噴鏀撅紝ADC鐨勭枟鏁堝拰瀹夊叏鎬у緱鍒颁簡鏄捐憲鎻愬崌銆傝繖浜涙妧鏈繘姝ユ瀬澶у湴鎵╁睍浜咟/span>ADC鐨勬不鐤楃獥鍙ｏ紝闄嶄綆浜嗚嵂鐗╁鍋ュ悍缁勭粐鐨勫壇浣滅敤锛屽悓鏃舵渶澶у寲浜嗗鐥呭彉缁勭粐鐨勬墦鍑诲姏搴︺€侟/span>

ADC鑽墿鐨勭爺鍙戞垚鏈瀬楂橈紝鍚屾椂闈复鐫€澶辫触椋庨櫓銆傝〃寰佸叧閿川閲忓睘鎬э紙CQAs锛夋槸闄嶄綆鐮斿彂椋庨櫓銆佹彁楂樹骇鍝佹垚鍔熺巼鐨勫叧閿墍鍦ㄣ€侟/span>

01涓?strong>鍏抽敭璐ㄩ噺灞炴€ц〃寰佺殑鎸戞垬涓庢満閬嘃/strong>

ADC鑽墿鐨勬垚鍔熶緷璧栦簬澶氫釜鍥犵礌锛屽寘鎷姉浣撲笌鎶楀師缁撳悎鍚庣殑鏁堟灉銆佽嵂鐗╄浇鑽峰鎶椾綋绋冲畾鎬х殑褰卞搷锛屼互鍙婅仛闆嗚涓虹瓑銆傚叾涓紝浠ヤ笅闂灏や负鍏抽敭锛欬/span>

1. 鍋惰仈瀵圭粨鍚堟椿鎬х殑褰卞搷锛欬/span>甯哥敤鐨勮禆姘ㄩ吀鍋惰仈绛栫暐鍙兘鏀瑰彉鎶椾綋鐨勭粨鍚堝尯鍩燂紝浠庤€岄檷浣庤嵂鐗╅澏鍚戞€т笌鐤楁晥銆侟/span>

2. 鎶椾綋绋冲畾鎬х殑闄嶄綆锛欬/span>鍋惰仈鐨勯珮鐤忔按鎬у皬鍒嗗瓙鑽墿寰€寰€浼氬奖鍝嶆姉浣撶殑缁撴瀯绋冲畾鎬э紝澧炲姞鑱氶泦鍊惧悜锛岀缉鐭嵂鐗╀繚璐ㄦ湡銆侟/span>

3. 浜氬井绫抽绮掔殑褰㈡垚锛欬/span>浜氬井绫抽绮掑彲鑳藉紩鍙戝厤鐤師鎬у弽搴旓紝鏄洃绠℃満鏋勬棩鐩婂叧娉ㄧ殑閲嶇偣銆侟/span>
   
   

闈㈠ADC鐮斿彂涓殑澶嶆潅鎸戞垬锛岄┈灏旀枃甯曠撼绉戞彁渚涗簡涓€绯诲垪鍏堣繘鐨勮〃寰佸伐鍏凤紝瑕嗙洊鐮斿彂鍏ㄨ繃绋嬶紝甯姪浼佷笟绉戝搴斿闂骞朵紭鍖栧紑鍙戞晥鐜囥€侟/span>

浠庣爺鍙戝埌鐢熶骇鐨勫叏绋嬫敮鎸?/span>

椹皵鏂囧笗绾崇鐨勬妧鏈笌涓撲笟鐭ヨ瘑璐┛ADC鑽墿鐨勭爺鍙戝叏杩囩▼锛屾棤璁烘槸璇勪及缁撳悎閮ㄤ綅涓庢椿鎬с€佷紭鍖栫ǔ瀹氭€э紝杩樻槸鎺у埗棰楃矑褰㈡垚锛岄兘鑳戒负浼佷笟鎻愪緵鍏ㄩ潰鏀寔銆傚湪杩欎釜鍏呮弧娼滃姏鐨勯鍩燂紝鎴戜滑鍔╁姏鐮斿彂浼佷笟鍦ㄦ彁楂樻晥鐜囧拰璐ㄩ噺鐨勫悓鏃讹紝闄嶄綆鐮斿彂澶辫触鐨勯闄╋紝甯姪鏇村鍒涙柊鐤楁硶閫犵鎮ｈ€呫€侟/span>