2023骞?鏈?鏃ワ紝娴庢皯鍙俊瀹e竷锛屾棗涓嬪瓙鍏徃涓婃捣娴庣厹鍖昏嵂绉戞妧鏈夐檺鍏徃鑷富鐮斿彂鐨勬敞灏勭敤JYB1907鏂拌嵂涓村簥璇曢獙鐢宠(IND)宸茶幏寰楃編鍥紽DA涓村簥璇曢獙璁稿彲銆?/p>
JYB1907鏄笂娴锋祹鐓滃ぇ鍒嗗瓙鍒涙柊鐮旂┒闄㈣嚜涓荤爺鍙戠殑闈跺悜GARP/ TGF-β1閲嶇粍浜烘簮鍖栧崟鍏嬮殕鎶椾綋鍒涙柊鑽紝鎷ユ湁鑷富鐭ヨ瘑浜ф潈锛屽睘鐢熺墿鍒跺搧1绫绘柊鑽紝鎷熺敤浜庢不鐤楀眬閮ㄦ櫄鏈熸垨杞Щ鎬у疄浣撶槫锛岃繖鏄浗鍐呯巼鍏堝湪缇庡浗鐢虫姤鑾锋壒涓村簥鐨凣ARP/ TGF-β1鍗曞厠闅嗘姉浣撹嵂鐗╋紝涓村簥璇曢獙鐢宠浜?022骞?1鏈?7鏃ヨ幏寰桭DA鍙楃悊锛?2鏈?7鏃ュ嵆鑾峰緱FDA涓村簥璇曢獙璁稿彲銆?/p>
绯栬泲鐧紸涓诲閲嶅搴忓垪(GARP)鏄綔浼忚浆鍖栫敓闀垮洜瀛?beta;1(LTGF-β1)鐨処鍨嬭法鑶滅粏鑳炶〃闈㈠鎺ュ彈浣擄紝鍦ㄦ椿鍖栫殑璋冭妭鎬缁嗚優(Tregs)鍜岃灏忔澘涓婂ぇ閲忚〃杈俱€侴APR鑳藉浠嬪杞寲鐢熼暱鍥犲瓙-β1(TGF-β1)鐨勯噴鏀撅紝鍦ㄨ偪鐦ゅ唴閮紝TGF-βs锛屽挨鍏舵槸TGF-β1锛屼細鍒烘縺鍩鸿川缁嗚優澧炵敓銆佹柊琛€绠″舰鎴愩€佺檶缁嗚優杞Щ鍙婃姂鍒跺厤鐤粏鑳炴蹈娑︺€傛柊鐮旂┒鍙戠幇锛孴GF-β鏄厤鐤鏌ョ偣鎶戝埗鍓傚湪鑲跨槫寰幆澧冧腑鑰愯嵂鐨勪富瑕佸師鍥犮€傚熀浜庢锛孏ARP/TGF-β1鏄疶reg缁嗚優鍏锋湁鍏嶇柅鎶戝埗鍔熻兘鐨勬牳蹇冩満鐞嗕箣涓€銆傛姂鍒惰偪鐦ゅ井鐜Treg缁嗚優琛ㄩ潰GARP閲婃斁TGF-β1鍔熻兘锛屾槸姝ら澏鐐逛富瑕佺殑鎴愯嵂鏈哄埗, 涔熸槸绮惧噯鍏嶇柅鑲跨槫娌荤枟瀵勪笌鍘氭湜鐨勬綔鍔涢澏鐐广€?/p>
JYB1907閫氳繃鐗瑰紓鎬х粨鍚圙ARP/ TGF-β1锛岄樆鏂璆ARP浠嬪鐨凾GF-β1鐨勯噴鏀撅紝閫嗚浆鑲跨槫寰幆澧冧腑鐨勫厤鐤姂鍒舵晥搴旓紝鎻愰珮鎶楄偪鐦ゅ厤鐤簲绛旓紝涓村簥鍓嶇爺绌剁粨鏋滄樉绀哄嚭鑹ソ鐨勫畨鍏ㄦ€у拰鏈夋晥鎬с€傚湪澶氱浜鸿偪鐦ょ粏鑳濸BMC浜烘簮鍖栬偪鐦ゅ姩鐗╂ā鍨嬩腑锛孞YB1907鍧囪〃鐜板嚭涓嶅悓绋嬪害鐨勮偪鐦ょ敓闀挎姂鍒朵綔鐢紝鍏朵腑鍦╖R-75-1浜轰钩鑵虹檶妯″瀷涓彲瑙傚療鍒拌秴杩囦竴鍗婃瘮渚嬬殑灏忛紶鑲跨槫瀹屽叏娑堥€€銆侸YB1907涓嶱D-L1鎶椾綋鑱旂敤锛屽湪A375浜洪粦鑹茬礌鐦ゆā鍨嬩腑璇卞浜嗛儴鍒嗗皬榧犺偪鐦ゅ畬鍏ㄦ秷閫€锛屾樉钁椾紭浜嶱D-L1鎶椾綋鍗曠敤鐨勬姂鐦ゆ晥鏋滐紝鏄剧ず鍑鸿仈鍚堢敤鑽叿鏈夎嵂鏁堝寮轰綔鐢ㄣ€?/p>
鐩墠锛屾祹姘戝彲淇″凡瀹屾垚JYB1907涓村簥鐮旂┒璁″垝锛屼互渚垮揩閫熸帹杩涗复搴奍鏈熻瘯楠岋紝鏃╂棩涓烘偅鑰呭甫鏉ョ闊炽€?/p>
鍙傝€冩枃鐚細
鈶燤etelli, Alessandra et al. “Immunoregulatory functions and the therapeutic implications of GARP-TGF-β in inflammation and cancer.” Journal of hematology & oncology. 2018, 11(1): 24
鈶atoh, Kazuki et al. “Novel anti-GARP antibody DS-1055a augments anti-tumor immunity by depleting highly suppressive GARP+ regulatory T cells.” International immunology. 2021, 33(8): 435-446.
鈶uende, Julia, et al. "Monoclonal antibodies against GARP/TGF-β1 complexes inhibit the immunosuppressive activity of human regulatory T cells in vivo." Science translational medicine. 2015, 7(284): 284ra56.
锛堣繍钀ワ細瀛欐锛?/p>
缃戝弸璇勮