{"id":69646,"date":"2022-06-15T16:29:00","date_gmt":"2022-06-15T09:29:00","guid":{"rendered":"https:\/\/www.xinwengao.com\/cn\/pr\/2022061516290069646"},"modified":"2022-06-15T22:57:17","modified_gmt":"2022-06-15T14:57:17","slug":"%e9%99%86%e9%81%93%e5%9f%b9%e5%8c%bb%e9%99%a2%e9%99%86%e4%bd%a9%e5%8d%8e%e9%99%a2%e9%95%bf%e6%9c%80%e6%96%b0%e7%a0%94%e7%a9%b6%e6%88%90%e6%9e%9c%e5%85%a5%e9%80%892022eha%e5%a4%a7%e4%bc%9a%e5%8f%a3","status":"publish","type":"post","link":"https:\/\/www.xinwengao.com\/cn\/pr\/2022061516290069646","title":{"rendered":"\u9646\u9053\u57f9\u533b\u9662\u9646\u4f69\u534e\u9662\u957f\u6700\u65b0\u7814\u7a76\u6210\u679c\u5165\u90092022EHA\u5927\u4f1a\u53e3\u5934\u62a5\u544a"},"content":{"rendered":"

\u5317\u4eac<\/span>2022\u5e746\u670815\u65e5<\/span> \/\u7f8e\u901a\u793e\/ — \u7b2c27\u5c4a\u6b27\u6d32\u8840\u6db2\u5b66\u5e74\u4f1a\uff08EHA\uff09\u4e8e2022\u5e746\u67089\u65e5-17\u65e5\u4ee5\u7ebf\u4e0a+\u7ebf\u4e0b\u7684\u65b9\u5f0f\u5982\u671f\u53ec\u5f00\uff0c\u4f5c\u4e3a\u5168\u7403\u8840\u6db2\u5b66\u9886\u57df\u89c4\u6a21\u6700\u5927\u7684\u56fd\u9645\u4f1a\u8bae\u4e4b\u4e00\uff0c\u6bcf\u5e74\u6765\u81ea100\u591a\u4e2a\u56fd\u5bb6\u7684\u4e0a\u4e07\u4f59\u540d\u8840\u6db2\u9886\u57df\u4e13\u4e1a\u4eba\u58eb\uff0c\u5206\u4eab\u548c\u63a2\u8ba8\u5168\u7403\u6700\u524d\u6cbf\u7684\u7814\u7a76\u8fdb\u5c55\u548c\u7a81\u7834\u6027\u4e34\u5e8a\u7814\u7a76\u6210\u679c\u3002\u672c\u5c4aEHA\u5927\u4f1a\uff0c\u9646\u9053\u57f9\u533b\u5b66\u56e2\u961f\u67095\u9879\u7814\u7a76\u6210\u679c\uff08\u5305\u62ec2\u7bc7\u53e3\u5934\u62a5\u544a\u30013\u7bc7\u5899\u62a5\u5c55\u793a\uff09\u5165\u9009\u3002<\/p>\n

\u9646\u9053\u57f9\u533b\u5b66\u56e2\u961f\u4f5c\u4e3a\u56fd\u5185\u8840\u6db2\u75c5\u9886\u57df\u7684\u4f7c\u4f7c\u8005\uff0c\u9664\u4e86\u5728ASH\u3001EBMT\u3001EHA\u7b49\u5927\u4f1a\u4e0a\u5f3a\u52bf\u53d1\u58f0\uff0c\u7814\u7a76\u6210\u679c\u53ca\u8bba\u6587\u66f4\u662f\u520a\u767b\u5728Blood\u3001American Journal of Hematology\u7b49\u8840\u6db2\u9886\u57df\u6743\u5a01\u671f\u520a\u4e0a\uff0c\u5c55\u793a\u51fa\u4e86\u56e2\u961f\u5353\u8d8a\u7684\u533b\u7597\u6280\u672f\u6c34\u5e73\u4ee5\u53ca\u5f3a\u5927\u7684\u79d1\u7814\u521b\u65b0\u80fd\u529b\u3002<\/p>\n

\u9646\u9053\u57f9\u533b\u9662\u533b\u7597\u6267\u884c\u9662\u957f\u9646\u4f69\u534e\u6559\u6388\u901a\u8baf\u4f5c\u8005\uff0c\u8840\u6db2\u79d1\u6768\u541b\u82b3\u4e3b\u4efb\u4e3a\u7b2c\u4e00\u4f5c\u8005\uff0c\u6458\u8981\u53f7\uff1aS110\uff0c\u9898\u4e3a\uff1aA novel and successful CD7 gene knockout CAR-T cell therapy for relapsed or refractory T-cell hematologic malignancies\uff08\u4e00\u79cd\u65b0\u578b\u57fa\u56e0\u6572\u9664\u7684CD7 CAR-T\u7ec6\u80de\u6cbb\u7597\u590d\u53d1\u6216\u96be\u6cbb\u6027T\u7ec6\u80de\u8840\u6db2\u80bf\u7624\u7684\u7814\u7a76\uff09\u7684\u7814\u7a76\u6210\u679c\u5165\u9009\u672c\u5c4aEHA\u5927\u4f1a\u53e3\u5934\u62a5\u544a\u3002<\/p>\n

\n

\"\"<\/a>
<\/span><\/p>\n<\/p><\/div>\n

\u9646\u4f69\u534e\u9662\u957f\u7684\u53e3\u5934\u62a5\u544a\u5f15\u8d77\u70ed\u70c8\u53cd\u54cd\uff0c\u4e0e\u4f1a\u5b66\u8005\u7eb7\u7eb7\u53d1\u8a00\u70ed\u60c5\u8ba8\u8bba\uff0c\u5e76\u8868\u793a\u8be5\u9879\u7814\u7a76\u6210\u679c\u5bf9\u4e8eT\u7ec6\u80de\u6076\u6027\u80bf\u7624\u60a3\u8005\u7684\u6cbb\u7597\u662f\u4e00\u4e2a\u8f83\u5927\u7684\u7a81\u7834\uff0c\u62a5\u544a\u4e2d\u7684\u6570\u636e\u4e0e\u7ed3\u8bba\u9f13\u821e\u4eba\u5fc3\u3002\u4f1a\u8bae\u7ed3\u675f\u540e\uff0c\u9646\u4f69\u534e\u9662\u957f\u6536\u5230\u4e86\u5f88\u591a\u6765\u81ea\u56fd\u5916\u540c\u4ec1\u7684\u90ae\u4ef6\u54a8\u8be2\uff0c\u6211\u4eec\u4e5f\u671f\u5f85\u4eca\u540e\u7ed9\u56fd\u5185\u5916\u8840\u6db2\u9886\u57df\u540c\u4ec1\u5e26\u6765\u66f4\u8fdb\u4e00\u6b65\u7684\u7814\u7a76\u6210\u679c\u3002<\/p>\n

\u7814\u7a76\u80cc\u666f<\/b><\/p>\n

T\u7ec6\u80de\u6076\u6027\u80bf\u7624\u662f\u4e00\u79cd\u590d\u53d1\u7387\u548c\u6b7b\u4ea1\u7387\u8f83\u9ad8\u7684\u8840\u6db2\u80bf\u7624\u3002\u7531\u4e8eCAR-T\u7ec6\u80de\u548c\u6076\u6027T\u7ec6\u80de\u5171\u540c\u8868\u8fbeCD7\u4f1a\u5bfc\u81f4CAR-T\u7ec6\u80de\u7684"\u81ea\u76f8\u6b8b\u6740"\uff0c\u56e0\u6b64\u8fd9\u5728\u4e00\u5b9a\u7a0b\u5ea6\u4e0a\u9650\u5236\u4e86CAR-T\u7ec6\u80de\u6cbb\u7597\u5728T\u7ec6\u80de\u6076\u6027\u80bf\u7624\u4e2d\u7684\u53d1\u5c55\u3002\u5728\u8fd9\u91cc\uff0c\u6211\u4eec\u901a\u8fc7CRISPR\/CAS9\u57fa\u56e0\u7f16\u8f91\u5f00\u53d1\u4e86\u4e00\u79cd\u4e0d\u4f1a\u4ea7\u751f"\u81ea\u76f8\u6b8b\u6740"\u7684KO7CAR-T\u7ec6\u80de\u3002<\/p>\n

\u7814\u7a76\u76ee\u6807<\/b><\/p>\n

\u5728\u4e00\u671f\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\uff0c\u6211\u4eec\u63a2\u7d22\u4e86KO7CAR-T\u7ec6\u80de\u6cbb\u7597\u590d\u53d1\u6216\u96be\u6cbb\u6027(R\/R) T\u7ec6\u80de\u6076\u6027\u80bf\u7624(NCT04916860\u548cNCT04938115)\u7684\u6709\u6548\u6027\u548c\u5b89\u5168\u6027\u3002<\/p>\n

\u7814\u7a76\u65b9\u6cd5<\/b><\/p>\n

\u901a\u8fc7\u5355\u91c7\u6536\u96c6\u60a3\u8005(n=13)\u548c\u79fb\u690d\u4f9b\u8005(n=2)\u7684\u5916\u5468\u8840\u5355\u4e2a\u6838\u7ec6\u80de\u3002\u5728\u8f6c\u67d3CD7CAR\u7684\u524d24\u5c0f\u65f6\uff0c\u901a\u8fc7CD7\u9776\u5411\u7684Cas9-gRNA RNP\u7535\u7a7f\u5b54T\u7ec6\u80de\uff0c\u6700\u7ec8\u83b7\u5f97\u6572\u9664CD7\u7684CAR-T\u7ec6\u80de\u3002KO7CAR-T\u662f\u9776\u5411CD7\u7684\u7b2c\u4e8c\u4ee3CAR-T\uff0c\u5171\u523a\u6fc0\u56e0\u5b50\u662f4-1BB\u548cCD3\u03b6\u3002\u5728\u8f93\u6ce8KO7CAR-T\u7ec6\u80de\u4e4b\u524d\u7684\u7b2c5\u5929\u81f3\u7b2c3\u5929\uff0c\u6240\u6709\u60a3\u8005\u90fd\u8fdb\u884c\u4e86\u9884\u5904\u7406\uff0c\u9759\u8109\u6ce8\u5c04\u6c1f\u8fbe\u62c9\u6ee8(30mg\/m2<\/sup>\/d)\u548c\u73af\u78f7\u9170\u80fa(300mg\/m2<\/sup>\/d)\u3002<\/p>\n

\u7814\u7a76\u7ed3\u679c<\/b><\/p>\n

\u4ece2020\u5e7410\u6708\u52302021\u5e7410\u6708\uff0c\u5171\u670915\u4f8b\u6025\u6027T\u6dcb\u5df4\u7ec6\u80de\u767d\u8840\u75c5(n=10)\u3001T\u7ec6\u80de\u6dcb\u5df4\u6bcd\u7ec6\u80de\u6dcb\u5df4\u7624(n=3)\u548c\u6df7\u5408\u8868\u578b\u6025\u6027\u767d\u8840\u75c5(n=2)\u60a3\u8005\u5165\u7ec4\u5e76\u63a5\u53d7\u4e86KO7 CAR-T\u7ec6\u80de\u6cbb\u7597\u3002\u5165\u7ec4\u60a3\u8005\u7684\u4e2d\u4f4d\u5e74\u9f84\u4e3a28(8-46)\u5c81\u30024\u4f8b\u60a3\u8005\u66fe\u63a5\u53d7\u8fc7\u9020\u8840\u5e72\u7ec6\u80de\u79fb\u690d\u3002\u5165\u7ec4\u65f6\uff0c10\u4f8b\u60a3\u8005\u7684\u9aa8\u9ad3\u5f62\u6001\u503c\u5927\u4e8e5%, 9\u4f8b\u60a3\u8005\u6709\u9ad3\u5916\u75c5\u7076(EMD\uff0c\u5176\u4e2d7\u4f8b\u662f\u5f25\u6f2b\u6027\u7d2f\u53ca\uff0c2\u4f8b\u662f\u5927\u4f53\u79ef\u7eb5\u9694\u80bf\u5757)\u3002\u6240\u6709\u60a3\u8005\u7684KO7 CAR-T\u7ec6\u80de\u5747\u6210\u529f\u5236\u5907\uff0c\u8f6c\u67d3\u7387\u7684\u4e2d\u4f4d\u503c\u4e3a59.0%(22.5%-97.4%)\u3002\u56de\u8f93\u5355\u5242\u91cf\u7684KO7CAR-T\u7ec6\u80de\uff0c\u5206\u4e3a\u4e09\u4e2a\u5242\u91cf\uff0c\u4f4e\u5242\u91cf(1.5~5×105<\/sup>cells\/kg, n=8)\uff0c\u4e2d\u5242\u91cf(1×106<\/sup>cells\/kg, n=6)\u6216\u9ad8\u5242\u91cf(2×106<\/sup>cells\/kg, n=1)\u3002<\/p>\n

\u5728KO7 CAR-T\u56de\u8f93\u540e\u7b2c28\u5929\u7684\u7597\u6548\u8bc4\u4f30\u4e2d\uff0c15\/15\u4f8b(100%)\u60a3\u8005\u90fd\u8fbe\u5230\u4e86\u6700\u5c0f\u6b8b\u7559\u75c5(MRD)\u9634\u6027\u7684\u5b8c\u5168\u7f13\u89e3(CR)\u3002\u5bf9\u4e8e9\u4f8b\u6709EMD\u7684\u60a3\u8005\uff0c\u5728\u56de\u8f93\u540e\u7b2c30\u5929\u7684\u9ad3\u5916\u8bc4\u4f30\u4e2d\uff0c6\u4f8b\u60a3\u8005\u8fbe\u5230CR, 2\u4f8b\u60a3\u8005\u8fbe\u5230\u90e8\u5206\u7f13\u89e3(PR)\uff0c \u53e6\u59161\u4f8b\u5c5e\u4e8e\u4e8c\u6b21\u79fb\u690d\u540e\u590d\u53d1\uff0c\u5728\u7b2c35\u5929\u7684\u9ad3\u5916\u8bc4\u4f30\u4e2d\u6ca1\u6709\u7f13\u89e3\uff0c\u7136\u540e\u51fa\u7ec4\u3002\u7814\u7a76\u7684\u622a\u6b62\u65f6\u95f4\u662f2022\u5e742\u670810\u65e5\uff0c\u4e2d\u4f4d\u968f\u8bbf\u65f6\u95f4\u4e3a309\u5929(35~407\u5929)\u3002KO7 CAR-T\u7ec6\u80de\u56de\u8f93\u540e2\u4e2a\u6708\u5de6\u53f3\uff0c12\u4f8b\u60a3\u8005\u6865\u63a5\u4e86\u5f02\u57fa\u56e0\u9020\u8840\u5e72\u7ec6\u80de\u79fb\u690d\uff0c\u9664\u4e861\u4f8b\u60a3\u8005\u7b2c217\u5929\u590d\u53d1\u540e\u5728\u7b2c249\u5929\u6b7b\u4e8e\u8111\u51fa\u8840\u5916\u4ee5\u5916\uff0c\u5269\u4e0b\u768411\u4f8b\u60a3\u8005\u4ecd\u7136\u5904\u4e8e\u7f13\u89e3\u72b6\u6001\uff0c\u79fb\u690d\u540e\u6301\u7eed\u7f13\u89e3\u7684\u4e2d\u4f4d\u65f6\u95f4\u4e3a253(30~388)\u5929\u30022\u4f8b\u5728KO7 CAR-T\u56de\u8f93\u540e\u6ca1\u6709\u6865\u63a5\u79fb\u690d\u7684\u60a3\u8005\uff08\u5728CAR-T\u6cbb\u7597\u4e4b\u524d\u66fe\u63a5\u53d7\u8fc7\u79fb\u690d)\uff0c\u5206\u522b\u5728KO7 CAR-T\u56de\u8f93\u540e\u7684\u7b2c78\u5929\u548c\u7b2c103\u5929\u6b7b\u4e8e\u611f\u67d3\u548cGVHD\u3002<\/p>\n

KO7 CAR-T\u56de\u8f93\u540e\uff0c\u6240\u6709\u7684\u60a3\u8005\u90fd\u53d1\u751f\u4e86\u7ec6\u80de\u56e0\u5b50\u91ca\u653e\u7efc\u5408\u5f81\uff08CRS\uff09\uff0c10\/15\u4f8b(66.7%)\u60a3\u8005\u53d1\u751f\u8f7b\u5ea6CRS\uff08\u5c0f\u4e8e\u7b49\u4e8e<\/span>II\u7ea7\uff09\uff0c5\/15\u4f8b(33.3%)\u60a3\u8005\u53d1\u751fIII\u7ea7CRS\u30023\u4f8b\u60a3\u8005\u53d1\u751f\u795e\u7ecf\u6bd2\u6027\uff0c\u5176\u4e2d1\u4f8b\u4e3aI\u7ea7\u795e\u7ecf\u6bd2\u6027\uff0c2\u4f8b\u4e3aIII\/IV\u7ea7\u795e\u7ecf\u6bd2\u6027\uff0c\u5728\u4f7f\u7528\u76ae\u8d28\u6fc0\u7d20\u548c\/\u6216\u6258\u73e0\u5355\u6297\u540e\u5747\u5f97\u5230\u63a7\u5236\u3002<\/p>\n

KO7 CAR-T\u56de\u8f93\u540e\uff0c\u901a\u8fc7q-PCR\u548c\u6d41\u5f0f\u7ec6\u80de\u4eea\u6765\u68c0\u6d4bCAR-T\u7ec6\u80de\u7684\u6269\u589e\u60c5\u51b5\uff0cq-PCR\u68c0\u6d4b\u5230\u7684KO7 CAR-T\u7ec6\u80de\u57fa\u56e0\u7ec4DNA\u7684\u4e2d\u4f4d\u5cf0\u503c\u4e3a1.77×105<\/sup> (0.279~14.3×105<\/sup>)copies\/\u03bcg\uff0c\u53d1\u751f\u5728\u7b2c20\u5929(10~25\u5929)\uff1b\u6d41\u5f0f\u68c0\u6d4b\u5230\u7684\u4e2d\u4f4dKO7 CAR-T\u7ec6\u80de\u6269\u589e\u7684\u4e2d\u4f4d\u5cf0\u503c\u4e3a63.47%(23.1%~94.18%)\uff0c\u53d1\u751f\u5728\u7b2c15\u5929(9~25\u5929)\u3002<\/p>\n

\u7ed3\u8bba<\/b><\/p>\n

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