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CAR-T缁嗚優娌荤枟鐨勪笅涓€涓墠娌匡細瀹炰綋鑲跨槫

瀹為獙瀹よ祫璁綉鏃堕棿:2019-04-13 鐐瑰嚮: 娆?/span> 鐧惧害鎼滅储

銆愬璇汇€?/strong>46宀佺殑Cecilia Barron姝ゅ埢鍜屽ス鐨勫効瀛愭鍦ㄦ礇鏉夌煻澶栫殑甯屾湜涔嬪煄(City of Hope)鐧岀棁鐮旂┒涓績鐨勪竴闂存埧闂撮噷绛夊緟鐫€銆?灏忔椂鍚庯紝鎶ゅ+浼氳蛋杩涙潵锛屽線濂瑰ご鐨笂鐨勮偪鍧楁敞灏勬暟鐧句竾涓猅缁嗚優銆侭arron鏄疌ostco鐨勮泲绯曡楗板笀锛屼笌涓堝か鍜屽瀛愪綇鍦ㄦ礇鏉夌煻銆傚ス浠?007骞村紑濮嬫不鐤楄剳鐧岋紝鎺ュ彈杩囧寲鐤椼€佹斁鐤楀拰澶氭鎵嬫湳銆傚湪杩囧幓鐨?0骞撮噷锛岀檶鐥囦竴......
TAG鏍囩锛?CaR-T 缁嗚優娌荤枟 CAR-T缁嗚優娌荤枟 瀹炰綋鑲跨槫
CAR-T缁嗚優娌荤枟鐨勪笅涓€涓墠娌匡細瀹炰綋鑲跨槫

46宀佺殑Cecilia Barron姝ゅ埢鍜屽ス鐨勫効瀛愭鍦ㄦ礇鏉夌煻澶栫殑甯屾湜涔嬪煄(City of Hope)鐧岀棁鐮旂┒涓績鐨勪竴闂存埧闂撮噷绛夊緟鐫€銆?灏忔椂鍚庯紝鎶ゅ+浼氳蛋杩涙潵锛屽線濂瑰ご鐨笂鐨勮偪鍧楁敞灏勬暟鐧句竾涓猅缁嗚優銆侭arron鏄疌ostco鐨勮泲绯曡楗板笀锛屼笌涓堝か鍜屽瀛愪綇鍦ㄦ礇鏉夌煻銆傚ス浠?007骞村紑濮嬫不鐤楄剳鐧岋紝鎺ュ彈杩囧寲鐤椼€佹斁鐤楀拰澶氭鎵嬫湳銆傚湪杩囧幓鐨?0骞撮噷锛岀檶鐥囦竴鐩存槸濂圭敓娲讳腑涓嶅彲鍒嗗壊鐨勪竴閮ㄥ垎銆?/p>

鍘诲勾澶忓ぉ锛孊arron鐨勭檶鐥囦粠绗簩闃舵鍙戝睍鍒扮涓夐樁娈靛皯绐佽兌璐ㄧ粏鑳炵槫銆傚ス鍦ㄥ笇鏈涗箣鍩庣殑澶栫鍖荤敓Behnam Badie鍛婅瘔濂癸紝濂规湁璧勬牸鎺ュ彈涓€椤瑰疄楠屾€ф不鐤?mdash;—鏀归€犲ス鑷繁鐨凾缁嗚優鑳藉璇嗗埆鑲跨槫缁嗚優琛ㄩ潰鎶楀師鐨勭粏鑳烇紝鐒跺悗娉ㄥ皠杩涘ス鐨勫ぇ鑴戙€傚綋涓嬶紝鍚湁杩欑宓屽悎鎶楀師鍙椾綋(CAR) T缁嗚優鐨勭枟娉曞凡缁忚鎵瑰噯鐢ㄤ簬娌荤枟涓€浜涜娑茬檶鐥囷紙濡傚ぇB缁嗚優娣嬪反鐦ゅ拰B缁嗚優鎬ユ€ф穻宸寸粏鑳炵櫧琛€鐥咃級锛屼絾杩欑鏂规硶鍦ㄦ不鐤楀儚Barron杩欐牱鐨勫疄浣撹偪鐦や笂娌℃湁閭d箞鎴愬姛銆?/p>

CAR-T缁嗚優娌荤枟鐨勪笅涓€涓墠娌匡細瀹炰綋鑲跨槫

Cecilia Barron

灏界濡傛锛屽尰鐢熶滑杩樻槸甯屾湜鑳芥壘鍒板悎閫傜殑鍓傞噺銆丆AR鏋勯€犲拰琛ュ厖鐤楁硶鏉ュ彂鎸ヤ綔鐢ㄣ€?ldquo;鍚捣鏉ュ緢鏈夊笇鏈涳紝” Barron璇达紝“浠讳綍浜嬫儏鍦ㄦ病鏈夊鍒ょ粨鏉熺殑鏃跺€欙紝鎴戦兘鎰挎剰灏濊瘯……鍞竴璁╂垜瀹虫€曠殑鏄拡銆?rdquo;

绱ф帴鐫€锛孊arron鍧愬湪鐥呭簥涓婏紝涓や釜鎶ゅ+鎷跨潃灏忕摱T缁嗚優璧颁簡杩涙潵銆傚叾涓竴涓敞灏勫埌濂逛竴涓湀鍓嶈鍒囬櫎鐨勫ぇ鑴戣厰锛屽彟涓€涓敞灏勫埌鑴戝鐨勮剳鑴婃恫銆傛敞鍏ョ粏鑳為渶瑕佸嚑鍒嗛挓锛岀劧鍚庢槸绛夊緟鐨勬椂闂淬€侭arron杩橀渶瑕佸嚑涓皬鏃舵墠鑳藉洖瀹讹紝鐒跺悗鏄嚑鍛ㄣ€佸嚑涓湀銆佺敋鑷虫洿闀挎椂闂存墠鑳界湅鍒板ス鐨勭檶鐥囨槸鍚︿細淇濇寔骞抽潤銆?/p>

2018骞?鏈堬紝鎺ュ彈CAR-T娌荤枟5涓湀鍚庯紝Barron鎰熻鑹ソ锛屽ス鐨勬牳纾佸叡鎸垚鍍忓拰PET鎵弿涔熸樉绀虹粨鏋滈潪甯稿ソ銆傚儚杩欐牱鐨勭Н鏋佽抗璞¤Barron鍜屽叾浠栦汉涔愯鍦拌涓篊AR-T鎶€鏈兘鏈夋晥鍦版潃姝诲疄浣撹偪鐦わ紝灏卞儚鏌愪簺琛€娑茬檶鐥囦竴鏍枫€傜洰鍓嶅凡缁忔湁涓€浜涗复搴婅瘯楠屽浜庢棭鏈熼樁娈碉紝鑷村姏浜庤儼鑵虹檶銆侀棿鐨槫銆佽偤鐧屻€佷钩鑵虹檶绛夌殑娌荤枟銆?/p>

鐒惰€岋紝杩欎簺鑲跨槫甯︽潵鐨勬寫鎴樻槸琛€娑插拰楠ㄩ珦鐧岀棁鎵€娌℃湁鐨勩€傞鍏堬紝瀹炰綋鐧岀棁鏈夌潃鍑轰簡鍚嶇殑鎭跺姡鐜锛氶吀鎬с€佷綆姘у拰鍏嶇柅鎶戝埗銆傝繖浣垮緱T缁嗚優寰堥毦娴告鼎骞跺湪瀹炰綋鐧屽潡涓瓨娲汇€傝偪鐦ょ殑寮傝川鎬т篃鎰忓懗鐫€鎵€閫夋嫨鐨凜AR涓嶄細涓庢瘡涓偪鐦ょ粏鑳炵粨鍚堛€?/p>

璐濆嫆鍖诲闄㈢殑Nabil Ahmed璇达紝“骞朵笉鏄垜鎮茶锛屼絾鏄疄浣撹偪鐦や笉鏄櫧琛€鐥呫€侰AR-Ts闇€瑕佸仛澶ч噺宸ヤ綔锛屾墠鑳芥樉绀哄嚭杩欑鏂规硶鐨勬湁鏁堟€с€?rdquo;

浠や汉闅句互缃俊

Barron鏄繃鍘诲嚑骞存潵鍦ㄥ笇鏈涗箣鍩庢帴鍙桟AR-Ts娌荤枟鐨勬暟鍗佸悕鑴戠檶鎮h€呬箣涓€銆傝繖浜涙偅鏈夎兌璐ㄦ瘝缁嗚優鐦わ紙鍙堢О4绾ф槦褰㈢粏鑳炵槫锛夌殑鎮h€呬腑锛屾湁璁稿浜哄凡缁忕敤灏戒簡鍚勭鍔炴硶锛岄潰涓寸潃涓ュ郴鐨勯鍚庛€?/p>

20骞村墠锛岀檶鐥囩敓鐗╁瀹禬aldemar Debinski鍦ㄥ宸炲窞绔嬪ぇ瀛﹀彂鐜板厤鐤俊鍙峰垎瀛愮櫧缁嗚優浠嬬礌13 (IL-13)鐨勫彈浣撳瓨鍦ㄤ簬鑳惰川姣嶇粏鑳炵槫涓紝浣嗕笉瀛樺湪浜庢甯哥殑鑴戠粍缁囦腑銆傚洜姝わ紝杩欑鍙椾綋浼间箮鏄竴涓緢濂界殑鐩爣锛屾棦鑳介攣瀹氱檶缁嗚優锛屽張鑳戒繚鎶ゅ仴搴风粏鑳炪€?/p>

2004骞?鏈堬紝甯屾湜涔嬪煄鐨勭爺绌跺皬缁勫皢CAR-T缁嗚優鐩存帴娉ㄥ皠鍒?涓兌璐ㄦ瘝缁嗚優鐦ゆ偅鑰呯殑澶ц剳涓€傜爺绌朵汉鍛樺湪鎮h€呮帴鍙楄緭娉ㄧ殑鍑犲懆鍐呮病鏈夎瀵熷埌鏄庢樉鐨勪笉鑹弽搴旓紝杩欐槸涓€涓噸瑕佺殑鎴愬氨銆傚洜涓篊AR-T鐤楁硶鐨勬渶澶х己鐐逛箣涓€灏辨槸鍙兘瀵艰嚧涓ラ噸鐨勫厤鐤繃搴﹀弽搴斻€備笌姝ゅ悓鏃讹紝鎮h€呯殑鐧岀棁涔熷嚭鐜颁簡涓€浜涚煭鏆傜殑鍙嶅簲锛屾瘮濡傝偪鐦ゆ浜$殑杩硅薄鍜孖L-13涓板害鐨勯檷浣庛€備絾娌℃湁鎮h€呯棅鎰堬細鎵€鏈変笁鍚嶆偅鑰呭湪鎺ュ彈娌荤枟涓€骞村唴姝讳骸銆傚笇鏈涗箣鍩庤剳鐦AR-T鐮旂┒璐熻矗浜篊hristine Brown琛ㄧず锛?ldquo;杩欒鎴戜滑鍦ㄨ繘琛屾洿澶ц妯$殑璇曢獙涔嬪墠锛屽CAR鏈韩杩涜浜嗕紭鍖栥€?rdquo;

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CAR-T缁嗚優娌荤枟鐨勪笅涓€涓墠娌匡細瀹炰綋鑲跨槫

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缁勫悎鐤楁硶鐨凜AR-Ts

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The Next Frontier of CAR T-Cell Therapy: Solid Tumors

Receptor for interleukin 13 is a marker and therapeutic target for human high-grade gliomas,” Clin Cancer Res, 5:985–90, 1999.

C.E. Brown et al., “Bioactivity and safety of IL13Rα2-redirected chimeric antigen receptor CD8+ T cells in patients with recurrent glioblastoma,” Clin Cancer Res, 21:4062–72, 2015.

C.E. Brown et al., “Regression of glioblastoma after chimeric antigen receptor T-cell therapy,” New Engl J Med, 375:2561–69, 2016.

N. Ahmed et al., “Human epidermal growth factor receptor 2 (HER2)–specific chimeric antigen receptor–modified T cells for the immunotherapy of HER2-positive sarcoma,” J Clin Oncol, 33:1688–96, 2015.

P.S. Adusumilli et al., “Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity,” Sci Transl Med, 6:261ra151, 2014.

P.S. Adusumilli et al., “A phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CAR T cells: Safety and efficacy - A preliminary report,” American Society of Cell & Gene Therapy 21st Annual Meeting, Chicago, May 17, 2018.

L. Cherkassky et al., “Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition,” J Clin Invest, 126:3130–44, 2016.

O.O. Yeku et al., “Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment,” Sci Rep, 7:10541, 2017.

B. Hu et al., “Augmentation of antitumor immunity by human and mouse CAR T cells secreting IL-18,” Cell Rep, 20:P3025–33, 2017.

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