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42.1 <\/strong>CAR-T\u7ec6\u80de\u548cTCR-T\u7ec6\u80de\u836f\u7269\u7684\u8fdc\u666f\u548c\u5386\u53f2<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u76ee\u524d\u9636\u6bb5\uff0c\u9884\u6d4b\u7a76\u7adf\u662fCAR\u8fd8\u662fTCR\u80fd\u591f\u4ee5\u6700\u9ad8\u6548\u3001\u5b89\u5168\u3001\u6709\u6548\u4e14\u53ef\u6301\u7eed\u7684\u65b9\u5f0f\u5f15\u5bfcT\u7ec6\u80de\u7528\u4e8e\u764c\u75c7\u6cbb\u7597\uff0c\u4ecd\u4e3a\u65f6\u8fc7\u65e9\u3002\u6bcf\u79cd\u65b9\u6cd5\u90fd\u6709\u5404\u81ea\u7684\u4f18\u7f3a\u70b9\uff0c\u56e0\u6b64\u5b83\u4eec\u53ef\u80fd\u4f1a\u5171\u5b58\uff0c\u5e76\u4e3a\u4e0d\u540c\u7c7b\u578b\u6216\u4eba\u7fa4\u7684\u764c\u75c7\u63d0\u4f9b\u670d\u52a1\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

TCR\u6cbb\u7597\u7684\u5173\u952e\u4f18\u52bf\u5728\u4e8e\uff0c\u6240\u6709\u86cb\u767d\u8d28\u90fd\u901a\u8fc7MHC\u5448\u9012\u7ed9T\u7ec6\u80de\uff0c\u56e0\u6b64\uff0c\u6240\u6709\u6f5c\u5728\u6297\u539f\u90fd\u5728TCR\u7684\u8bc6\u522b\u8303\u56f4\u5185\u3002\u800c\u5bf9\u4e8eCAR\u6cbb\u7597\uff0c\u4ec5\u7ec6\u80de\u8868\u9762\u6297\u539f\u53ef\u88ab\u8bc6\u522b\uff0c\u8fd9\u53ea\u6db5\u76d6\u4e86\u4e0d\u523010%\u7684\u6f5c\u5728\u9776\u70b9\uff0c\u4e14\u4e0d\u8003\u8651\u8868\u9762\u53ef\u53ca\u6027\u7b49\u56e0\u7d20\u3002CAR\u6cbb\u7597\u7684\u4e3b\u8981\u4f18\u52bf\u5728\u4e8e\u5176\u6297\u539f\u8bc6\u522b\u662f\u76f4\u63a5\u7684\uff0c\u4e0d\u9700\u8981\u4f9d\u8d56MHC\uff0c\u56e0\u6b64\u5355\u4e2aCAR\u53ef\u9002\u7528\u4e8e\u6240\u6709\u60a3\u8005\u7fa4\u4f53\uff0c\u800cTCR\u5219\u53ea\u80fd\u4e0e\u7279\u5b9aMHC\u5206\u5b50\u7ed3\u5408\u5f62\u6210\u590d\u5408\u7269\u6765\u8bc6\u522b\u76ee\u6807\u80bd\u3002\u7531\u4e8eMHC\u7684\u9ad8\u5ea6\u591a\u6001\u6027\uff0cTCR\u6cbb\u7597\u53d7\u9650\u4e8e\u4ec5\u80fd\u5e94\u7528\u4e8e\u8868\u8fbe\u7279\u5b9aMHC\u5206\u5b50\u7684\u60a3\u8005\u3002\u6b64\u5916\uff0c\u80bf\u7624\u901a\u8fc7\u4e22\u5931\u6216\u4e0b\u8c03\u6297\u539f\u5904\u7406\u9014\u5f84\u6216MHC\u6765\u9003\u907f\u514d\u75ab\u5e94\u7b54\u662fTCR\u6cbb\u7597\u7684\u6311\u6218\uff0c\u800cCAR\u6cbb\u7597\u5219\u4e0d\u5b58\u5728\u6b64\u7c7b\u95ee\u9898\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n


<\/p>\n<\/section>\n<\/section>\n

\n
\n

42.2 TCR\/CAR\u7684\u6765\u6e90<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u76ee\u524d\uff0c\u7edd\u5927\u591a\u6570CAR\u7ed3\u6784\u90fd\u91c7\u7528\u4e86scFv\u7ed3\u6784\u4f5c\u4e3a\u5176\u6297\u539f\u9776\u5411\u7247\u6bb5\uff0c\u5176\u4e2d\u8bb8\u591a\u6765\u6e90\u4e8e\u5355\u514b\u9686\u6297\u4f53\u7684\u518d\u5229\u7528\u3002\u8fd9\u4e9b\u6297\u4f53\u5df2\u88ab\u8bc1\u660e\u662f\u6cbb\u7597\u836f\u7269\uff0c\u53ef\u5355\u72ec\u4f7f\u7528\u6216\u4f5c\u4e3a\u6297\u4f53\u836f\u7269\u5076\u8054\u7269\u3002\u7136\u800c\uff0c\u4efb\u4f55\u4e0e\u76ee\u6807\u6297\u539f\u7ed3\u5408\u5177\u6709\u8db3\u591f\u9ad8\u4eb2\u548c\u529b\u548c\u7279\u5f02\u6027\u7684\u7ed3\u5408\u5143\u7d20\uff0c\u90fd\u53ef\u4ee5\u7528\u4e8e\u6a21\u5757\u5316\u7684CAR\u6784\u5efa\u3002\u4e8b\u5b9e\u4e0a\uff0c\u5728\u9488\u5bf9\u53d7\u4f53\u65f6\uff0c\u53ef\u4ee5\u4f7f\u7528\u914d\u4f53\uff0c\u6b63\u5982\u5728IL-13\u201czetakine\u201d CAR\u4e2d\u7684\u5e94\u7528\uff0c\u5b83\u5305\u542b\u4e86\u7ecf\u8fc7\u7a81\u53d8\u7684\u91cd\u7ec4IL-13\uff0c\u4ee5\u589e\u5f3a\u4e0e\u80bf\u7624\u76f8\u5173\u7684IL13R\u03b12\u7684\u4eb2\u548c\u529b\uff0c\u540c\u65f6\u51cf\u5c11\u4e0eIL13R\u03b11\u7684\u7ed3\u5408\uff0c\u4ece\u800c\u907f\u514d\u4e0e\u66f4\u5e7f\u6cdb\u8868\u8fbe\u7684\u53d7\u4f53\u4ea7\u751f\u4f5c\u7528\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u4f7f\u7528\u5c0f\u9f20\u6765\u6e90\u7684scFv\u53ef\u80fd\u4f1a\u56e0\u4e3a\u4ea7\u751f\u4eba\u6297\u5c0f\u9f20\u6297\u4f53\uff08HAMA\uff09\u800c\u9650\u5236\u5176\u6301\u4e45\u6027\uff0c\u5e76\u4e14\u5728\u67d0\u4e9b\u60c5\u51b5\u4e0b\u53ef\u80fd\u5e26\u6765\u5b89\u5168\u98ce\u9669\u3002\u5982\u679c\u4ea7\u751f\u4e86IgE\u578bHAMA\uff0c\u53ef\u80fd\u5bfc\u81f4\u8fc7\u654f\u6027\u4f11\u514b\u7b49\u4e25\u91cd\u53cd\u5e94\u3002\u76f8\u6bd4\u4e4b\u4e0b\uff0c\u4eba\u6e90\u5316\u6216\u5b8c\u5168\u4eba\u6e90\u5316\u7684\u7ed3\u5408\u7269\u80fd\u591f\u6709\u6548\u51cf\u5c11HAMA\u7684\u98ce\u9669\uff0c\u56e0\u6b64\u5728\u67d0\u4e9b\u60c5\u51b5\u4e0b\u53ef\u80fd\u66f4\u4e3a\u7406\u60f3\u5e76\u5f97\u5230\u5e7f\u6cdb\u5e94\u7528\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

TCRs \u53ef\u4ee5\u4ece\u591a\u4e2a\u6765\u6e90\u83b7\u53d6\u3002\u6700\u521d\u7684TCR\u57fa\u56e0\u5de5\u7a0b\u514d\u75ab\u7597\u6cd5\u4f7f\u7528\u6765\u81ea\u81ea\u7136\u53d1\u751f\u7684\u60a3\u8005\u6216\u4f9b\u4f53T\u7ec6\u80de\u7684TCR\u3002\u5728\u6cbb\u7597\u8f6c\u79fb\u6027\u9ed1\u8272\u7d20\u7624\u7684\u4e34\u5e8a\u5b9e\u8df5\u4e2d\uff0c\u8bc6\u522b\u9ed1\u8272\u7d20\u7624\u6297\u539f1\uff08MART-1\uff09\u7684TCR\uff08\u5982DMF4 TCR\u548c\u9ad8\u4eb2\u548c\u529b\u7684DMF5 TCR\uff09\u662f\u4ece\u5bf9TIL\u6cbb\u7597\u4ea7\u751f\u4e34\u5e8a\u53cd\u5e94\u7684\u60a3\u8005\u4e2d\u83b7\u53d6\u7684\u3002\u7406\u8bba\u4e0a\uff0c\u7531\u4e8e\u81ea\u7136\u60c5\u51b5\u4e0bTCR\u91cd\u7ec4\u7684\u8303\u56f4\u975e\u5e38\u5e7f\u6cdb\uff0c\u4efb\u4f55\u4e2a\u4f53\u90fd\u6709\u53ef\u80fd\u62e5\u6709\u8bc6\u522b\u5176MHC\u4e0a\u51e0\u4e4e\u4efb\u4f55\u6297\u539f\u7684T\u7ec6\u80de\u7684TCR\u3002\u7136\u800c\uff0c\u4e0e\u6b63\u5e38\u81ea\u8eab\u86cb\u767d\u8d28\u5177\u6709\u9ad8\u4eb2\u548c\u529b\u7684TCR\u4f1a\u901a\u8fc7\u80f8\u817a\u7684\u8d1f\u6027\u9009\u62e9\u4eceTCR\u5e93\u4e2d\u5220\u9664\uff0c\u8fd9\u4f7f\u5f97\u5f88\u96be\u627e\u5230\u81ea\u7136\u53d1\u751f\u7684\u3001\u5bf9\u80bf\u7624\u6297\u539f\u5177\u6709\u8db3\u591f\u9ad8\u4eb2\u548c\u529b\u7684TCR\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\n
\n

\u8fd9\u79cd\u60c5\u51b5\u5c24\u5176\u5728\u5171\u4eab\u6297\u539f\u7684\u60c5\u51b5\u4e0b\u5c24\u4e3a\u7a81\u51fa\uff0c\u4f8b\u5982\u53d1\u80b2\u6297\u539f\uff08\u5982\u80ce\u513f\u764c\u80da\u6297\u539f\uff08CEA\uff09\uff09\u6216\u5206\u5316\u6297\u539f\uff08\u5982\u7cd6\u86cb\u767d100\uff08gp100\uff09\uff09\uff0c\u4ee5\u53ca\u5176\u4ed6\u80bf\u7624\u76f8\u5173\u6297\u539f\uff0c\u5982\u8fc7\u8868\u8fbe\u7684\u751f\u957f\u56e0\u5b50\u53d7\u4f53\uff08\u5305\u62ecERB\/HER\u6297\u539f\uff09\u3002\u901a\u5e38\uff0c\u8fd9\u4e9b\u201c\u81ea\u8eab\u201dTCR\u7684\u7ed3\u5408\u4eb2\u548c\u529b\u4ec5\u5728\u9ad8\u03bcM\u8303\u56f4\uff0c\u800c\u76f8\u6bd4\u4e4b\u4e0b\uff0c\u5355\u514b\u9686\u6297\u4f53\uff08mAb\uff09\u7684\u4eb2\u548c\u529b\u5219\u5728nM\u5230pM\u4e4b\u95f4\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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\n

\u867d\u7136\u5076\u5c14\u53ef\u4ee5\u4ece\u201c\u4f18\u79c0\u53cd\u5e94\u8005\u201d\u60a3\u8005\u4e2d\u5206\u79bb\u51fa\u9488\u5bf9\u5171\u4eab\u80bf\u7624\u6297\u539f\uff08\u5982MART-1\uff09\u7684\u9ad8\u4eb2\u548c\u529bTCR\uff0c\u4f46\u5927\u591a\u6570\u60c5\u51b5\u4e0b\uff0c\u8fd9\u4e9bTCR\u53ea\u80fd\u63d0\u4f9b\u4e00\u4e2a\u521d\u59cb\u6846\u67b6\uff0c\u5fc5\u987b\u901a\u8fc7\u9010\u6b65\u6c28\u57fa\u9178\u66ff\u6362\u548c\u5b9e\u9a8c\u6d4b\u8bd5\u6765\u589e\u5f3a\u4eb2\u548c\u529b\u3002\u4e00\u4e2a\u5178\u578b\u7684\u4f8b\u5b50\u662fc259 TCR\uff0c\u5b83\u8bc6\u522b\u7531HLA-A*02\u5448\u9012\u7684NY-ESO-1\uff08157-165\uff09SLLMWITQC\u80bd\u3002\u8868\u8fbe\u8fd9\u79cdTCR\u7684TCR T\u7ec6\u80de\u5728\u6076\u6027\u9ed1\u8272\u7d20\u7624\u548c\u68ad\u5f62\u7ec6\u80de\u8089\u7624\u60a3\u8005\u4e2d\u5206\u522b\u8fbe\u5230\u4e8650%\u548c80%\u7684\u5ba2\u89c2\u53cd\u5e94\u7387\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5f53\u65e0\u6cd5\u4ece\u6b63\u5e38\u4ebaT\u7ec6\u80de\u4e2d\u83b7\u5f97\u8db3\u591f\u9ad8\u4eb2\u548c\u529b\u7684TCR\u65f6\uff0c\u53ef\u4ee5\u4eceHLA-A*02\u8f6c\u57fa\u56e0\u5c0f\u9f20\u6216HLA-A*02\/\u4ebaTCR\u53cc\u8f6c\u57fa\u56e0\u5c0f\u9f20\u4e2d\u83b7\u53d6\u66f4\u9ad8\u4eb2\u548c\u529b\u7684TCR\u53d8\u5f02\u4f53\u3002\u4e3a\u786e\u4fdd\u8fd9\u79cd\u65b9\u6cd5\u6210\u529f\uff0c\u76ee\u6807\u6297\u539f\u4e0d\u80fd\u4e0e\u5c0f\u9f20\u540c\u6e90\uff0c\u8fd9\u6837\u53ef\u4ee5\u8ba9\u5c0f\u9f20\u5c06MHC-\u80bd\u590d\u5408\u7269\u89c6\u4e3a\u201c\u975e\u81ea\u8eab\u201d\u3002\u901a\u8fc7\u8fd9\u79cd\u65b9\u5f0f\uff0c\u80fd\u591f\u751f\u6210\u4e0e\u76ee\u6807\u80bd-MHC\u590d\u5408\u7269\u7ed3\u5408\u7684\u9ad8\u4eb2\u548c\u529bTCR\uff0c\u800c\u8fd9\u4e9bTCR\u5728\u80f8\u817a\u9009\u62e9\u8fc7\u7a0b\u4e2d\u4e0d\u4f1a\u88ab\u5220\u9664\u3002\u63a5\u7740\uff0c\u53ef\u4ee5\u901a\u8fc7\u514d\u75ab\u5c0f\u9f20\u4ee5\u6240\u9700\u7684\u86cb\u767d\u8d28\u6216\u80bd\uff0c\u968f\u540e\u4ece\u6dcb\u5df4\u5668\u5b98\u4e2d\u5206\u79bb\u51faT\u7ec6\u80de\uff0c\u5728\u4f53\u5916\u8fdb\u4e00\u6b65\u523a\u6fc0\u548c\u6269\u589e\u6297\u539f\u9633\u6027T\u7ec6\u80de\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\n


<\/p>\n<\/section>\n<\/section>\n

\n
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42.3 \u4e3aCAR T\u7ec6\u80de\u548cTCR T\u7ec6\u80de\u5bfb\u627e\u5408\u9002\u9776\u70b9\u7684\u6311\u6218<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u8bc6\u522b\u9002\u5408CAR T\u7ec6\u80de\u548cTCR T\u7ec6\u80de\u6cbb\u7597\u7684\u5408\u9002\u9776\u70b9\u662f\u4e00\u9879\u590d\u6742\u4e14\u5177\u6709\u6311\u6218\u6027\u7684\u4efb\u52a1\u3002\u5373\u4f7f\u662f\u90a3\u4e9b\u5df2\u7ecf\u5728\u764c\u75c7\u75ab\u82d7\u7814\u7a76\u4e2d\u5e7f\u6cdb\u63a2\u7d22\uff0c\u6216\u4f5c\u4e3a\u5355\u514b\u9686\u6297\u4f53\u548c\u6297\u4f53\u836f\u7269\u7ed3\u5408\u7269\u9776\u70b9\u7684\u6297\u539f\uff08\u5982MAGE-A3\u548cHer2neu\uff09\uff0c\u5728\u5e94\u7528\u4e8eCAR\u6216TCR\u6cbb\u7597\u65f6\u4e5f\u9762\u4e34\u65b0\u7684\u6311\u6218\u3002\u8fd9\u53ef\u80fd\u6e90\u4e8eT\u7ec6\u80de\u5f3a\u6548\u6fc0\u6d3b\uff0c\u4ee5\u53ca\u5408\u6210\u514d\u75ab\u53d7\u4f53\u5f15\u53d1\u7684\u610f\u5916\u4ea4\u53c9\u53cd\u5e94\u6a21\u5f0f\u3002\u8fd9\u4f7f\u5f97\u8bc6\u522b\u5408\u9002\u6297\u539f\u7684\u5de5\u4f5c\u53d8\u5f97\u66f4\u52a0\u590d\u6742\uff0c\u5c24\u5176\u662f\u56e0\u4e3a\u52a8\u7269\u6a21\u578b\u5728CAR\u548cTCR\u6cbb\u7597\u7684\u5b89\u5168\u7b5b\u9009\u65b9\u9762\u5e76\u4e0d\u9002\u7528\u3002\u8fd9\u662f\u56e0\u4e3a\u8bb8\u591a\u6297\u539f\u5728\u5c0f\u9f20\u548c\u4eba\u7c7b\u4e4b\u95f4\u4e0d\u5171\u4eab\uff0c\u5e76\u4e14\u4e24\u8005\u7684MHC\u80cc\u666f\u5b8c\u5168\u4e0d\u540c\u3002\u5373\u4f7f\u4f7f\u7528\u4e86\u4eba\u6e90\u5316\u5c0f\u9f20\u6a21\u578b\uff0c\u6297\u539f\u7684\u8868\u8fbe\u8c31\u548c\u4ea4\u53c9\u53cd\u5e94\u8c31\u4e5f\u5f88\u96be\u51c6\u786e\u53cd\u6620\u4eba\u7c7b\u7684\u60c5\u51b5\u3002\u56e0\u6b64\uff0c\u5728\u4eba\u4f53\u8bd5\u9a8c\u4e2d\u89c2\u5bdf\u5230\u7684\u795e\u7ecf\u6bd2\u6027\u3001\u4e25\u91cd\u7684\u7ec6\u80de\u56e0\u5b50\u91ca\u653e\u7efc\u5408\u5f81\u4ee5\u53ca\u5176\u4ed6\u4e00\u7cfb\u5217\u6bd2\u6027\u53cd\u5e94\uff0c\u5f80\u5f80\u5728\u5c0f\u9f20\u7814\u7a76\u4e2d\u65e0\u6cd5\u9884\u6d4b\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5728\u7b2c\u4e00\u4ee3\u6210\u529f\u7684CAR T\u7ec6\u80de\u7597\u6cd5\u4e2d\uff0c\u9776\u5411CD19\u6297\u539f\u6210\u529f\u89c4\u907f\u4e86\u80bf\u7624\u7279\u5f02\u6027\u6297\u539f\u6240\u56fa\u6709\u7684\u6311\u6218\u3002CD19\u5728\u6574\u4e2aB\u7ec6\u80de\u7cfb\u4e2d\u5e7f\u6cdb\u8868\u8fbe\uff0c\u4f7f\u5176\u5728B\u7ec6\u80de\u6076\u6027\u80bf\u7624\u7684\u540e\u671f\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u663e\u793a\u51fa\u663e\u8457\u7597\u6548\u3002\u7531\u4e8eB\u7ec6\u80de\u65e0\u529b\u75c7\uff08B\u7ec6\u80de\u529f\u80fd\u4e27\u5931\uff09\u53ef\u4ee5\u901a\u8fc7\u8f93\u6ce8\u9759\u8109\u514d\u75ab\u7403\u86cb\u767d\u6765\u90e8\u5206\u8865\u507f\uff0c\u56e0\u6b64\u4e0d\u4f1a\u5bfc\u81f4\u4e25\u91cd\u7684\u514d\u75ab\u7f3a\u9677\u3002\u968f\u540e\u5f00\u53d1\u7684CAR T\u7ec6\u80de\u7597\u6cd5\u4e5f\u91c7\u7528\u4e86\u7c7b\u4f3c\u7b56\u7565\uff0c\u9776\u5411\u9650\u4e8eB\u7ec6\u80de\u7cfb\u7684\u989d\u5916\u6297\u539f\uff08\u5982BCMA\u3001CD20\u3001CD22\u548c\u03ba\u8f7b\u94fe\uff09\uff0c\u8fdb\u4e00\u6b65\u6269\u5c55\u4e86\u5bf9B\u7ec6\u80de\u6076\u6027\u80bf\u7624\u7684\u6cbb\u7597\u8303\u56f4\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
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\u7136\u800c\uff0c\u9488\u5bf9\u975eB\u7ec6\u80de\u8840\u6db2\u6076\u6027\u80bf\u7624\u6216\u5b9e\u4f53\u80bf\u7624\uff0c\u5c1a\u672a\u627e\u5230\u7c7b\u4f3c\u7684\u7406\u60f3\u9776\u70b9\u3002\u4ee5\u9ed1\u8272\u7d20\u7ec6\u80de\u5206\u5316\u6297\u539fMART-1\u548cgp100\u4e3a\u4f8b\uff0c\u5c3d\u7ba1\u5b83\u4eec\u5728\u9ed1\u8272\u7d20\u7624\u4e2d\u9ad8\u8868\u8fbe\u5e76\u4e14\u88ab\u8ba4\u4e3a\u662f\u826f\u597d\u7684\u80bf\u7624\u6392\u65a5\u6297\u539f\uff0c\u76f8\u5173\u7684TCR T\u7ec6\u80de\u7597\u6cd5\u5374\u8868\u73b0\u51fa\u8f83\u4f4e\u7684\u5ba2\u89c2\u53cd\u5e94\u7387\uff0c\u4e14\u4f34\u968f\u66f4\u5927\u7684\u6bd2\u526f\u4f5c\u7528\uff0c\u6548\u679c\u8fdc\u4e0d\u53ca\u81ea\u4f53\u80bf\u7624\u6d78\u6da6\u6dcb\u5df4\u7ec6\u80de\u7597\u6cd5\u3002\u56e0\u6b64\uff0c\u8fd9\u7c7b\u6297\u539f\u7684\u5e94\u7528\u9700\u7279\u522b\u8c28\u614e\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
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\u5230\u76ee\u524d\u4e3a\u6b62\uff0cTCR T\u7ec6\u80de\u9886\u57df\u5728\u76ee\u6807\u6297\u539f\u7684\u9009\u62e9\u4e0a\u5927\u91cf\u501f\u9274\u4e86\u764c\u75c7\u75ab\u82d7\u7814\u7a76\u7684\u7ecf\u9a8c\u3002Table 42.1<\/span>\u603b\u7ed3\u4e86\u8fdb\u5165\u4e34\u5e8a\u8bd5\u9a8c\u7684TCR T\u7ec6\u80de\u9776\u5411\u6297\u539f\uff0c\u800cFig 42.1<\/span>\u5c55\u793a\u4e86\u4e0d\u540c\u6cbb\u7597\u8def\u5f84\u7684\u6570\u91cf\u53ca\u5176\u5f00\u53d1\u9636\u6bb5\u3002\u663e\u7136\uff0c\u8fc4\u4eca\u4e3a\u6b62\u6709\u4e09\u7c7b\u6297\u539f\u5360\u636e\u4e3b\u5bfc\u5730\u4f4d\uff1a\u764c\u80da\u7cfb\u6297\u539f\u3001\u75c5\u6bd2\u6297\u539f\u548c\u5206\u5316\u6297\u539f\uff0c\u540e\u8005\u5728\u80bf\u7624\u4e2d\u8fc7\u8868\u8fbe\uff0c\u4f46\u4e5f\u5b58\u5728\u4e8e\u6b63\u5e38\u91cd\u8981\u7ec4\u7ec7\u4e2d\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u75c5\u6bd2\u6297\u539f\u88ab\u8ba4\u4e3a\u662f\u6700\u5b89\u5168\u7684\u9776\u70b9\u4e4b\u4e00\uff0c\u4f46\u5176\u9002\u5e94\u75c7\u4ec5\u9650\u4e8e\u7531\u75c5\u6bd2\u611f\u67d3\u9a71\u52a8\u7684\u80bf\u7624\uff0c\u4f8b\u5982\u4e0e\u4eba\u4e73\u5934\u7624\u75c5\u6bd2\uff08HPV\uff09\u6216\u4e59\u578b\u809d\u708e\u75c5\u6bd2\uff08HBV\uff09\u76f8\u5173\u7684\u80bf\u7624\u3002EBV\u548cCMV\u7279\u5f02\u6027CTL\u5df2\u88ab\u7528\u4e8e\u9884\u9632\u79fb\u690d\u540e\u6dcb\u5df4\u589e\u751f\u6027\u75be\u75c5\uff0c\u4f46\u8fd9\u4e9b\u7597\u6cd5\u4e3b\u8981\u901a\u8fc7\u81ea\u7136CTL\u7684\u6269\u589e\uff0c\u800c\u975eTCR\u57fa\u56e0\u8f6c\u79fb\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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\u764c\u80da\u7cfb\u6297\u539f\u5177\u6709\u6f5c\u529b\u4f5c\u4e3a\u9776\u70b9\uff0c\u56e0\u4e3a\u5b83\u4eec\u7684\u8868\u8fbe\u901a\u5e38\u4ec5\u9650\u4e8e\u80ce\u513f\u53d1\u80b2\u9636\u6bb5\uff0c\u4e14\u751f\u6b96\u7ec6\u80de\u7f3a\u4e4fHLA-I\u8868\u8fbe\uff0c\u65e0\u6cd5\u5411T\u7ec6\u80de\u5448\u9012\u6297\u539f\u3002\u4f8b\u5982\uff0cPRAME\u5728\u5065\u5eb7\u7ec4\u7ec7\u4e2d\u7684\u8868\u8fbe\u6c34\u5e73\u8f83\u4f4e\u3002\u7136\u800c\uff0c\u67d0\u4e9b\u764c\u80da\u7cfb\u6297\u539f\u7279\u5f02\u6027\u7684TCR T\u7ec6\u80de\u5728\u4e34\u5e8a\u4e2d\u56e0\u4ea4\u53c9\u53cd\u5e94\u5bfc\u81f4\u60a3\u8005\u6b7b\u4ea1\uff0c\u663e\u793a\u51fa\u6f5c\u5728\u7684\u5b89\u5168\u9690\u60a3\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\n

\u7b2c\u4e09\u7c7b\u662f\u5206\u5316\u6297\u539f\uff0c\u8fd9\u4e9b\u6297\u539f\u5728\u80bf\u7624\u4e2d\u7684\u8fc7\u8868\u8fbe\u76f8\u5bf9\u4e8e\u5176\u5065\u5eb7\u7ec4\u7ec7\u7684\u8868\u8fbe\u5177\u6709\u7279\u5f02\u6027\u3002\u6700\u6df1\u5165\u7814\u7a76\u7684\u6297\u539f\u5305\u62ec\u5728\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u4e2d\u7684EGFR\u3001\u4e73\u817a\u764c\u4e2d\u7684HER2neu\u3001\u524d\u5217\u817a\u764c\u4e2d\u7684PSMA\u548cPSCA\uff0c\u4ee5\u53ca\u6076\u6027\u9ed1\u8272\u7d20\u7624\u4e2d\u7684gp100\u548cmelan-A\/MART-1\u3002\u7136\u800c\uff0c\u5bf9\u4e8e\u540e\u4e24\u8005\uff0c\u7531\u4e8e\u5b83\u4eec\u5728\u5065\u5eb7\u76ae\u80a4\u4e2d\u7684\u8868\u8fbe\uff0c\u5bfc\u81f4\u4e86\u4e25\u91cd\u7684\u6bd2\u6027\u53cd\u5e94\uff0c\u8fd9\u8868\u660e\u5f53\u524d\u7684\u6280\u672f\u5c1a\u672a\u80fd\u5728\u5065\u5eb7\u7ec4\u7ec7\u548c\u80bf\u7624\u7ec4\u7ec7\u4e4b\u95f4\u5efa\u7acb\u8db3\u591f\u5b89\u5168\u7684\u9776\u5411\u7a97\u53e3\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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<\/section>\n<\/section>\n
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<\/p>\n<\/section>\n<\/section>\n

\n
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Table 42.1<\/span> \u5217\u51fa\u4e86TCR T\u7ec6\u80de\u5728\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u7684\u9776\u5411\u6297\u539f<\/span><\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
<\/section>\n<\/section>\n
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<\/p>\n<\/section>\n<\/section>\n

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Fig 42.1<\/span> \u5c55\u793a\u4e86CAR T\u7ec6\u80de\u548cTCR T\u7ec6\u80de\u6cbb\u7597\u7684\u901a\u8def\u3002\u5230\u76ee\u524d\u4e3a\u6b62\uff0cCAR T\u7ec6\u80de\u7684\u5f00\u53d1\u8def\u5f84\u6bd4TCR T\u7ec6\u80de\u66f4\u4e3a\u5e7f\u6cdb\u4e14\u6210\u719f\u3002\u968f\u7740CD19\u9776\u5411\u7597\u6cd5\u7684\u6210\u529f\uff0c\u5176\u4ed6B\u7ec6\u80de\u7cfb\u6297\u539f\uff08\u5982BCMA\u3001CD20\u3001CD22\u548c\u514d\u75ab\u7403\u86cb\u767dkappa\u94fe\uff09\u5360\u636e\u4e86\u4e3b\u5bfc\u5730\u4f4d\uff0c\u800cCD30\u867d\u7136\u4e25\u683c\u6765\u8bf4\u662f\u4e00\u79cdTAA\uff0c\u4f46\u6b63\u88ab\u7528\u4e8e\u9776\u5411B\u7ec6\u80de\u6076\u6027\u80bf\u7624\uff08\u5982\u970d\u5947\u91d1\u6dcb\u5df4\u7624\u548c\u975e\u970d\u5947\u91d1\u6dcb\u5df4\u7624\uff09\u3002\u4e0e\u6b64\u540c\u65f6\uff0c\u80bf\u7624\u751f\u6b96\u7cfb\u6297\u539f\u5728TCR T\u7ec6\u80de\u6cbb\u7597\u8def\u5f84\u4e2d\u5360\u636e\u4e3b\u5bfc\u5730\u4f4d\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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\u5728\u73b0\u6709\u7684TCR T\u7ec6\u80de\u7597\u6cd5\u4e2d\uff0c\u9664\u4e86\u5df2\u4f7f\u7528\u7684\u6297\u539f\u7c7b\u522b\u5916\uff0c\u8fd8\u6709\u51e0\u4e2a\u6f5c\u5728\u7684\u9776\u70b9\u7c7b\u522b\u5177\u6709\u5de8\u5927\u524d\u666f\uff0c\u5176\u4e2d\u5305\u62ec\u60a3\u8005\u7279\u5f02\u6027\u65b0\u8868\u4f4d\uff08neoepitopes\uff09\uff0c\u5982\u5f02\u5e38\u7684\u4e0e\u80bf\u7624\u76f8\u5173\u7684\u7ffb\u8bd1\u540e\u4fee\u9970\u4ee5\u53ca\u4e0e\u80bd\u5904\u7406\u53d7\u635f\u76f8\u5173\u7684T\u7ec6\u80de\u8868\u4f4d\uff08TEIPP\uff09\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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\u968f\u7740\u6df1\u5ea6\u6d4b\u5e8f\u3001\u8d28\u8c31\u548c\u751f\u7269\u4fe1\u606f\u5b66\u6280\u672f\u7684\u8fdb\u6b65\uff0c\u6211\u4eec\u73b0\u5728\u80fd\u591f\u9274\u5b9a\u51fa\u7279\u5b9a\u60a3\u8005\u80bf\u7624\u4e2d\u72ec\u7279\u7684\u65b0\u8868\u4f4d\uff0c\u5e76\u4ece\u60a3\u8005\u8840\u6db2\u4e2d\u6269\u589e\u51fa\u80fd\u591f\u8bc6\u522b\u8fd9\u4e9b\u79c1\u6709\u80bf\u7624\u7a81\u53d8\u7684\u81ea\u4f53T\u7ec6\u80de\u3002\u8fd9\u4e0d\u4ec5\u4e3a\u5b9e\u65bd\u591a\u514b\u9686TIL\u6837\u7597\u6cd5\u63d0\u4f9b\u4e86\u53ef\u884c\u6027\uff0c\u8fd8\u53ef\u80fd\u5e2e\u52a9\u53d1\u73b0\u4e0e\u66f4\u5927\u60a3\u8005\u7fa4\u4f53\u5171\u4eab\u7684\u65b0\u8868\u4f4d\uff0c\u7528\u4e8eTCR T\u7ec6\u80de\u7597\u6cd5\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u867d\u7136\u8bb8\u591a\u65b0\u8868\u4f4d\u6e90\u4e8e\u6c28\u57fa\u9178\u66ff\u4ee3\u3001\u79fb\u7801\u7a81\u53d8\u6216\u4ea4\u66ff\/\u9690\u79d8\u7684\u5f00\u653e\u9605\u8bfb\u6846\u67b6\uff0c\u4f46\u6700\u8fd1\u7684\u7814\u7a76\u53d1\u73b0\uff0c\u7531\u78f7\u9178\u80bd\u548c\u7cbe\u6c28\u9178\uff08\u53cc\uff09\u7532\u57fa\u5316\u80bd\u5f15\u8d77\u7684\u7ffb\u8bd1\u540e\u4fee\u9970\u7684\u6539\u53d8\u4e5f\u662f\u6709\u524d\u666f\u7684\u9776\u70b9\u7c7b\u522b\u3002\u8fd9\u7c7b\u9776\u70b9\u6709\u671b\u5728\u66f4\u591a\u60a3\u8005\u4e2d\u5171\u4eab\uff0c\u56e0\u4e3a\u5b83\u4eec\u4e0d\u4f9d\u8d56\u4e8e\u7279\u5b9a\u7a81\u53d8\uff0c\u800c\u662f\u4f9d\u8d56\u4e8e\u80bf\u7624\u4e2d\u5e38\u89c1\u7684\u7ffb\u8bd1\u540e\u4fee\u9970\u53d8\u5316\u3002\u4e8b\u5b9e\u4e0a\uff0c\u5f02\u5e38\u7684\u86cb\u767d\u78f7\u9178\u5316\u662f\u80bf\u7624\u7ec6\u80de\u7684\u4e00\u4e2a\u91cd\u8981\u7279\u5f81\uff0c\u4ea7\u751f\u4e86\u8bb8\u591a\u78f7\u9178\u80bd\u6297\u539f\uff0c\u5e76\u4e14\u5e38\u89c4\u03b1\u03b2 T\u7ec6\u80de\u80fd\u591f\u6709\u6548\u533a\u5206\u8fd9\u4e9b\u78f7\u9178\u80bd\u4e0e\u5176\u975e\u78f7\u9178\u5316\u7684\u5bf9\u5e94\u7269\u3002\u8fd9\u4f7f\u5f97\u7ffb\u8bd1\u540e\u4fee\u9970\u7684\u6297\u539f\u6210\u4e3a\u672a\u6765TCR T\u7ec6\u80de\u7597\u6cd5\u4e2d\u7684\u5173\u952e\u9776\u70b9\uff0c\u5177\u6709\u5e7f\u6cdb\u7684\u5e94\u7528\u6f5c\u529b\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5728TILs\u6216\u6cbb\u7597\u6027TCR T\u7ec6\u80de\u7684\u9009\u62e9\u538b\u529b\u4e0b\uff0c\u80bf\u7624\u53ef\u80fd\u901a\u8fc7\u8868\u89c2\u9057\u4f20\u6216\u57fa\u56e0\u7a81\u53d8\u4e27\u5931\u6216\u4e0b\u8c03\u6297\u539f\u5448\u9012\uff0c\u4ece\u800c\u4ea7\u751f\u6297\u6027\u53d8\u4f53\u3002\u8fd9\u79cdHLA\u57fa\u56e0\u7f3a\u5931\u4f7f\u80bf\u7624\u5bf9T\u7ec6\u80de\u7597\u6cd5\u5177\u6709\u62b5\u6297\u529b\uff0c\u4f46\u540c\u65f6\u53ef\u80fd\u4f7f\u5176\u5bf9NK\u7ec6\u80de\u66f4\u52a0\u8106\u5f31\u3002\u9664\u4e86MHC\u7684\u53d8\u5316\u5916\uff0c\u5176\u4ed6\u6297\u539f\u5904\u7406\u9014\u5f84\u7ec4\u5206\u7684\u4e0b\u8c03\u6216\u4e27\u5931\u4e5f\u5e38\u88ab\u89c2\u5bdf\u5230\uff0c\u8fd9\u53ef\u80fd\u662f\u80bf\u7624\u9003\u907f\u514d\u75ab\uff08T\u7ec6\u80de\u548cNK\u7ec6\u80de\uff09\u7684\u4e00\u79cd\u7b56\u7565\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\n
\n

\u7136\u800c\uff0c\u5728MHC\u8868\u8fbe\u4f46\u6297\u539f\u5904\u7406\u7f3a\u9677\u7684\u80bf\u7624\u4e2d\uff0c\u53ef\u80fd\u4f1a\u5448\u73b0\u4e00\u7ec4\u72ec\u7279\u4e14\u5e7f\u6cdb\u5171\u4eab\u7684\u76ee\u6807\u80bd-TEIPP\u3002\u8fc4\u4eca\u4e3a\u6b62\uff0c\u5408\u9002\u7684\u8868\u4f4d\u4ec5\u5728\u5c0f\u9f20\u4e2d\u88ab\u9274\u5b9a\u51fa\u3002\u4f8b\u5982\uff0c\u6297\u539f\u5904\u7406\u8f6c\u8fd0\u4f53\uff08TAP\uff09\u7f3a\u9677\u7684\u7ec6\u80de\u4e0a\uff0c\u867d\u7136MHC I\u7c7b\u5206\u5b50\u5448\u73b0\u7684\u80bd\u6c34\u5e73\u8f83\u4f4e\uff0c\u4f46\u4ecd\u4f1a\u5c55\u793a\u6765\u81eaTRH4\u86cb\u767d\u7684\u80bd\u3002\u5728\u6b63\u5e38\u60c5\u51b5\u4e0b\uff0cTRH4\u80bd\u4e0eMHC I\u7c7b\u5206\u5b50Db\u7684\u7ed3\u5408\u4f1a\u88ab\u7ec6\u80de\u4e2d\u66f4\u9ad8\u4eb2\u548c\u529b\u7684\u80bd\u6240\u7ade\u4e89\uff0c\u4f46\u5728\u7f3a\u4e4fTAP\u65f6\uff0c\u8db3\u591f\u591a\u7684TRH4-Db\u80bd\u590d\u5408\u7269\u5c06\u51fa\u73b0\u5728\u7ec6\u80de\u8868\u9762\uff0c\u5e76\u80fd\u591f\u6fc0\u6d3b\u9ad8\u4eb2\u548c\u529b\u7684T\u7ec6\u80de\u514b\u9686\u3002\u8fd9\u4e9bT\u7ec6\u80de\u514b\u9686\u4e4b\u6240\u4ee5\u5b58\u5728\uff0c\u662f\u56e0\u4e3a\u5728\u8d1f\u6027\u80f8\u817a\u9009\u62e9\u4e2d\uff0c\u5b83\u4eec\u672a\u66fe\u9047\u5230\u8fd9\u4e9b\u80bd-MHC\u590d\u5408\u7269\uff08\u7531\u4e8eTAP\u6b63\u5e38\u8868\u8fbe\u7684\u60c5\u51b5\u4e0b\u65e0\u6cd5\u5448\u9012\uff09\uff0c\u4ece\u800c\u9003\u8131\u4e86\u88ab\u5220\u9664\u7684\u547d\u8fd0\u3002
<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5c3d\u7ba1CAR T\u7ec6\u80de\u9886\u57df\u5c1d\u8bd5\u4e86\u8bb8\u591a\u4e0e\u764c\u75c7\u75ab\u82d7\u76f8\u540c\u7684\u6297\u539f\uff0c\u4f46\u4e00\u4e2a\u5173\u952e\u9650\u5236\u662fCAR\u53ea\u80fd\u9776\u5411\u7ec6\u80de\u8868\u9762\u6297\u539f\u3002\u76ee\u524d\u5df2\u6709\u6210\u529f\u9776\u5411B\u7ec6\u80de\u6076\u6027\u80bf\u7624\u7684\u4f8b\u5b50\uff0c\u5229\u7528B\u7ec6\u80de\u8c31\u7cfb\u7279\u5f02\u6027\u9776\u70b9\uff0c\u8fd9\u4e9b\u9776\u70b9\u5177\u6709\u76f8\u5bf9\u8f83\u5c11\u7684\u6570\u91cf\u4f46\u8f83\u9ad8\u7684\u5b89\u5168\u6027\uff0c\u56e0\u6b64\u8be5\u9886\u57df\u7ade\u4e89\u6fc0\u70c8\uff08Fig 42.1<\/span>\uff09\u3002\u6b64\u5916\uff0c\u9488\u5bf9\u80bf\u7624\u76f8\u5173\u6297\u539f\u548c\u5206\u5316\u6297\u539f\u7684\u7814\u7a76\u4e5f\u5728\u6301\u7eed\u8fdb\u884c\uff0c\u672a\u6765\u51e0\u5e74\u9884\u8ba1\u4f1a\u6709\u66f4\u591a\u7684\u4e34\u5e8a\u6570\u636e\u51fa\u73b0\uff08\u89c1Table 42.2<\/span>\u548cFig 42.1<\/span>\uff09\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
<\/section>\n<\/section>\n
\n
\n
\n


<\/p>\n<\/section>\n<\/section>\n

\n
\n

Table 42.2<\/span> CAR-T \u7ec6\u80de\u5728\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u9776\u5411\u7684\u6297\u539f<\/span><\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u603b\u7ed3\u800c\u8a00\uff0c\u76ee\u524d\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u5df2\u9274\u5b9a\u51fa\u591a\u4e2a\u5408\u9002\u7684\u9776\u70b9\uff0c\u5e76\u4e14\u5728\u975e\u4e34\u5e8a\u548c\u4e34\u5e8a\u9636\u6bb5\u7684\u7814\u7a76\u4e2d\uff0c\u79d1\u5b66\u5bb6\u4eec\u6b63\u79ef\u6781\u63a2\u7d22\u66f4\u5e7f\u6cdb\u7684\u9776\u70b9\u9009\u62e9\u7a7a\u95f4\u3002\u6b64\u5916\uff0c\u4ecd\u7136\u6709\u8bb8\u591a\u65b0\u7684\u6216\u8f83\u5c11\u7814\u7a76\u7684\u9776\u70b9\u7c7b\u522b\uff0c\u5305\u62ec\u672a\u6765\u53ef\u80fd\u5229\u7528\u7684\u7a81\u53d8\u65b0\u6297\u539f\uff0c\u8fd9\u4e9b\u9886\u57df\u5177\u6709\u5de8\u5927\u7684\u5f00\u53d1\u6f5c\u529b\u3002<\/p>\n

\u8fd9\u4e9b\u8fdb\u5c55\u4f7f\u6211\u4eec\u5bf9\u672a\u6765\u5145\u6ee1\u4fe1\u5fc3\u3002\u5728\u63a5\u4e0b\u6765\u7684\u51e0\u5e74\u91cc\uff0c\u8d8a\u6765\u8d8a\u591a\u7684\u9776\u70b9\u5c06\u88ab\u7528\u4e8e\u591a\u79cd\u764c\u75c7\u7684\u6cbb\u7597\uff0c\u4ece\u800c\u586b\u8865\u73b0\u6709\u7a7a\u767d\uff0c\u5e76\u63a8\u52a8\u836f\u7269\u5f00\u53d1\u7684\u8fdb\u7a0b\u3002\u5728\u6211\u4eec\u63a2\u8ba8\u9650\u5236\u5de5\u7a0bT\u7ec6\u80de\u5728\u80bf\u7624\u5b66\u4e2d\u5e7f\u6cdb\u5e94\u7528\u7684\u5176\u4ed6\u4e24\u4e2a\u5173\u952e\u6311\u6218\u4e4b\u524d\uff0c\u5fc5\u987b\u5f3a\u8c03CAR T\u7ec6\u80de\u548cTCR T\u7ec6\u80de\u7597\u6cd5\u5728\u975e\u4e34\u5e8a\u548c\u4e34\u5e8a\u5f00\u53d1\u4e2d\u7684\u5173\u952e\u7279\u70b9\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n


<\/p>\n<\/section>\n<\/section>\n

\n
\n

42.4 \u975e\u4e34\u5e8a\u5f00\u53d1<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u901a\u8fc7\u975e\u4e34\u5e8a\u5f00\u53d1\uff0c\u6539\u9020\u540e\u7684CAR\u548cTCR\u4fee\u9970T\u7ec6\u80de\u6210\u4e3a\u4e86\u4e00\u79cd\u201c\u9996\u521b\u7684\u6d3b\u4f53\u836f\u7269\u201d\u3002\u4f20\u7edf\u7684\u8bc4\u4f30\u65b9\u6cd5\uff0c\u5982\u7528\u4e8e\u5c0f\u5206\u5b50\u6291\u5236\u5242\u3001\u75ab\u82d7\u548c\u5355\u514b\u9686\u6297\u4f53\u6cbb\u7597\u7684\u751f\u7269\u5236\u5242\u8bc4\u4f30\uff0c\u5747\u4e0d\u9002\u7528\u4e8e\u8fd9\u7c7b\u7ec6\u80de\u7597\u6cd5\u3002\u5373\u4fbf\u662f\u7528\u4e8e\u8bc4\u4f30\u8f93\u8840\u6216\u9aa8\u9ad3\u79fb\u690d\u7684\u5e38\u89c4\u65b9\u6cd5\uff0c\u4e5f\u65e0\u6cd5\u5b8c\u5168\u9002\u5e94\u8fd9\u7c7b\u65b0\u5174\u7597\u6cd5\u3002\u8fd1\u5e74\u6d8c\u73b0\u7684\u7b2c\u4e09\u7c7b\u836f\u7269\uff0c\u5982\u7528\u4e8e\u6cbb\u7597\u7f55\u89c1\u75be\u75c5\u7684\u57fa\u56e0\u7597\u6cd5\uff0c\u4e3a\u5355\u57fa\u56e0\u7f3a\u9677\u60a3\u8005\u5e26\u6765\u4e86\u6cbb\u7597\u5e0c\u671b\uff0c\u800cCAR\u548cTCR T\u7ec6\u80de\u514d\u75ab\u7597\u6cd5\u5219\u7ed3\u5408\u4e86\u4e0a\u8ff0\u6240\u6709\u9886\u57df\u7684\u5143\u7d20\uff0c\u9996\u6b21\u5c06\u5b83\u4eec\u6574\u5408\u5728\u4e00\u8d77\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u8fd9\u79cd\u7597\u6cd5\u501f\u7528\u4e86\u751f\u7269\u5236\u836f\u4e2d\u5355\u514b\u9686\u6297\u4f53\u7684\u7ed3\u5408\u533a\u57df\uff0c\u540c\u65f6\u901a\u8fc7\u57fa\u56e0\u5de5\u7a0b\u5229\u7528\u4e86\u8f6c\u5316\u8f7d\u4f53\uff08\u5982\u4f3d\u9a6c\u9006\u8f6c\u5f55\u75c5\u6bd2\u6216\u6162\u75c5\u6bd2\uff09\uff0c\u5c06\u9776\u5411\u53d7\u4f53\u4e0e\u529f\u80fd\u57fa\u56e0\u76f8\u7ed3\u5408\u3002\u6240\u6709\u8fd9\u4e9b\u6280\u672f\u5171\u540c\u4f5c\u7528\uff0c\u901a\u8fc7\u4f53\u5916\u6539\u9020\u60a3\u8005\u7684T\u6dcb\u5df4\u7ec6\u80de\uff0c\u751f\u6210\u4e86\u4e00\u79cd\u4f9d\u8d56\u4e8e\u6570\u5343\u5e74\u8fdb\u5316\u6765\u5bf9\u6297\u4f53\u5185\u75be\u75c5\u7684\u201c\u6d3b\u4f53\u836f\u7269\u201d\uff0c\u5176\u5728\u8fd9\u91cc\u7684\u76ee\u6807\u662f\u764c\u75c7\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5f00\u53d1\u4efb\u4f55\u975e\u4e34\u5e8aCAR\u6216TCR\u7597\u6cd5\u90fd\u5fc5\u987b\u7ecf\u5386\u51e0\u4e2a\u5173\u952e\u6b65\u9aa4\u3002\u9996\u5148\u8981\u8003\u8651\u7684\u662f\u9776\u70b9\uff0cT\u7ec6\u80de\u9776\u70b9\u5e94\u5728\u9002\u5f53\u6bd4\u4f8b\u7684\u80bf\u7624\u7ec4\u7ec7\u4e0a\u8868\u8fbe\uff0c\u800c\u4e0d\u5e94\u5728\u5173\u952e\u7684\u6b63\u5e38\u7ec4\u7ec7\u4e0a\u51fa\u73b0\u3002\u5bf9\u6b64\uff0c\u4e00\u4e2a\u4f8b\u5b50\u662f\u9996\u4f4d\u63a5\u53d7\u6cbb\u7597\u768439\u5c81\u8f6c\u79fb\u6027\u9ed1\u8272\u7d20\u7624\u5973\u6027\u60a3\u8005\u3002\u5979\u63a5\u53d7\u4e86\u5927\u91cf\uff0810\u00b9\u2070\u4e2a\uff09\u81ea\u4f53HER2 CAR T\u7ec6\u80de\uff0c\u4f46\u5c3d\u7ba1\u8d85\u8fc740\u4e07\u540d\u4e73\u817a\u764c\u60a3\u8005\u63a5\u53d7\u4e86\u6297HER2\u5355\u514b\u9686\u6297\u4f53\uff08\u66f2\u59a5\u73e0\u5355\u6297\uff09\u4e14\u526f\u4f5c\u7528\u8f83\u5c0f\uff0c\u8fd9\u540d\u60a3\u8005\u5728\u63a5\u53d7\u4e86\u540c\u6837\u91cd\u5b9a\u5411\u7684HER2 CAR T\u7ec6\u80de\u540e\uff0c\u51fa\u73b0\u4e86\u4e25\u91cd\u547c\u5438\u7a98\u8feb\u5e76\u5728\u591a\u5668\u5b98\u529f\u80fd\u8870\u7aed\u540e\u4e0d\u5e78\u53bb\u4e16\u3002\u8fd9\u4e9b\u75c7\u72b6\u5728\u8f93\u6ce8\u540e15\u5206\u949f\u5185\u8fc5\u901f\u51fa\u73b0\uff0c\u660e\u786e\u8868\u660e\u4e86\u88f8\u6297\u4f53\u4e0e\u7ed3\u5408T\u7ec6\u80de\u4fe1\u53f7\u533a\u57df\u7684\u6297\u4f53\u4e4b\u95f4\u7684\u663e\u8457\u5dee\u5f02\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5c3d\u7ba1\u53ef\u4ee5\u901a\u8fc7\u964d\u4f4eCAR\u53d7\u4f53\u4eb2\u548c\u529b\u6216\u6709\u9650\u7ed9\u836f\u9014\u5f84\u6765\u7f13\u89e3\u90e8\u5206\u98ce\u9669\uff0c\u4ece\u800c\u9009\u62e9\u6027\u6467\u6bc1\u9ad8\u6297\u539f\u8868\u8fbe\u7684\u80bf\u7624\u5e76\u4fdd\u62a4\u4f4e\u6297\u539f\u8d1f\u8377\u7684\u6b63\u5e38\u7ec4\u7ec7\uff0c\u4f46\u6700\u5b89\u5168\u7684\u7b56\u7565\u4ecd\u662f\u9776\u5411\u771f\u6b63\u7684\u80bf\u7624\u7279\u5f02\u6027\u6297\u539f\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u76ee\u524d\uff0c\u591a\u79cd\u65b9\u6cd5\u5df2\u88ab\u91c7\u7528\u6765\u8bc6\u522b\u80bf\u7624\u7684\u4e34\u5e8a\u524d\u9776\u70b9\u3002\u6700\u521d\uff0c\u8bb8\u591a\u673a\u6784\u4f9d\u8d56\u81ea\u5df1\u7684\u80bf\u7624\u5e93\uff0c\u901a\u8fc7\u514d\u75ab\u7ec4\u5316\uff08IHC\uff09\u6216\u57fa\u56e0\u8868\u8fbe\u7684\u9006\u8f6c\u5f55\u805a\u5408\u9176\u94fe\u53cd\u5e94\uff08RT-PCR\uff09\u6765\u68c0\u6d4b\u6297\u539f\u3002\u7136\u800c\uff0c\u8fd1\u5e74\u6765\uff0c\u57fa\u4e8e\u751f\u7269\u4fe1\u606f\u5b66\u7684\u8d44\u6e90\u53d8\u5f97\u5e7f\u6cdb\u53ef\u7528\uff0c\u5c24\u5176\u662f\u901a\u8fc7\u516c\u5f00\u7684Human Protein Atlas\uff08proteinatlas.org\uff09\u6216The Cancer Genome Atlas\uff08TCGA\uff09\uff08cancergenome.nih.gov\uff09\u8fdb\u884c\u8bc4\u4f30\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5728\u9776\u70b9\u9009\u62e9\u540e\uff0c\u901a\u5e38\u9700\u8981\u8bbe\u8ba1\u7ed3\u5408\u7269\uff0c\u8fd9\u4e00\u7ed3\u5408\u7269\u901a\u5e38\u662f\u5355\u514b\u9686\u6297\u4f53\uff08mAb\uff09\u7684\u5355\u94fe\u6297\u4f53\u53d8\u4f53\uff08scFv\uff09\u3002\u4e00\u65e6\u9009\u62e9\u597d\u7ed3\u5408\u7269\u6216scFv\uff0c\u5c06\u5176\u5de5\u7a0b\u5316\u4e3a\u5305\u542b\u8fde\u63a5\u5668\u3001\u94f0\u94fe\/\u8de8\u819c\u7ed3\u6784\u57df\uff08\u901a\u5e38\u6765\u81eaCD4\u3001CD8\u6216IgG\uff09\u7684DNA\u6784\u5efa\u7269\uff0c\u968f\u540e\u518d\u6dfb\u52a0\u81f3\u5c11\u4e00\u4e2a\u5171\u523a\u6fc0\u5206\u5b50\u548cCD3\u03b6\u3002\u5c3d\u7ba1\u6709\u8d8a\u6765\u8d8a\u591a\u7684\u65b0\u5143\u7d20\u88ab\u52a0\u5165\uff0c\u4f46\u6700\u4f4e\u8981\u6c42\u4ecd\u662f\u4e0a\u8ff0\u7ec4\u5206\u3002CAR\u548cTCR\u7684\u5173\u952e\u533a\u522b\u5728\u4e8e\uff0cTCR\u9700\u8981\u8868\u8fbe\u5339\u914d\u7684\u5b8c\u6574CD3\u03b1\u548c\u03b2\u94fe\uff0c\u5305\u62ec\u6bcf\u6761\u94fe\u7684\u6052\u5b9a\u533a\u548c\u53ef\u53d8\u533a\uff0c\u53ea\u6709\u5728\u6b63\u786e\u914d\u5bf9\u65f6\u624d\u80fd\u5b9e\u73b0\u6297\u539f\u8bc6\u522b\u5e76\u6fc0\u6d3b\u5b8c\u6574\u7684CD3\u4fe1\u53f7\u901a\u8def\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\n
\n

\u5728\u4f53\u5916\u5b9e\u9a8c\u4e2d\uff0c\u91cd\u7ec4\u7684TCR\u6216CAR\u5728\u4f9b\u4f53T\u7ec6\u80de\u4e2d\u8868\u8fbe\uff0c\u786e\u8ba4\u8868\u9762\u8868\u8fbe\u540e\uff0c\u8fd9\u4e9b\u7ec6\u80de\u5c06\u8fdb\u884c\u7279\u5f02\u6027\u8bc6\u522b\u548c\u529f\u80fd\u6d4b\u8bd5\u3002\u6d4b\u8bd5\u65f6\u81f3\u5c11\u9700\u8981\u8bc4\u4f30\u5df2\u77e5\u7684\u6297\u539f\u9633\u6027\u548c\u6297\u539f\u9634\u6027\u9776\u7ec6\u80de\uff0c\u5b9e\u9645\u4e0a\uff0c\u901a\u5e38\u4f1a\u4f7f\u7528\u591a\u79cd\u4e0d\u540c\u80bf\u7624\u7c7b\u578b\u7684\u7ec6\u80de\u7cfb\u8fdb\u884c\u8bc4\u4f30\u3002\u5b9e\u9a8c\u529f\u80fd\u6d4b\u8bd5\u5927\u4f53\u5206\u4e3a\u4e24\u7c7b\uff1a(1)\u6548\u5e94T\u7ec6\u80de\u523a\u6fc0\u6216(2)\u9776\u7ec6\u80de\u7834\u574f\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u901a\u8fc7\u521d\u6b65\u7684\u7279\u5f02\u6027\u6d4b\u8bd5\u540e\uff0c\u63a5\u4e0b\u6765\u8fdb\u884c\u7684\u662f\u5b89\u5168\u6027\u8bc4\u4f30\uff0c\u4e3b\u8981\u5305\u62ec\u4e24\u79cd\u7c7b\u578b\uff1a(1)\u9776\u70b9\u53ef\u80fd\u4e5f\u5728\u975e\u80bf\u7624\u7ec4\u7ec7\u4e2d\u8868\u8fbe\uff0c\u6216(2)\u975e\u7279\u5f02\u6027\u6bd2\u6027\uff0c\u5373\u53d7\u4f53\u8bc6\u522b\u4e86\u975e\u76ee\u6807\u6297\u539f\u3002\u6bcf\u79cd\u5b89\u5168\u6027\u6d4b\u8bd5\u90fd\u9762\u4e34\u6311\u6218\uff0c\u9700\u8981\u5bf9\u4e0d\u540c\u7ec6\u80de\/\u7ec4\u7ec7\u7c7b\u578b\u7684\u57fa\u56e0\u8868\u8fbe\u8fdb\u884c\u5206\u6790\u3002\u5728\u68c0\u6d4b\u201c\u9776\u70b9\u4f5c\u7528\u4e8e\u975e\u80bf\u7624\u7ec4\u7ec7\u201d\u65f6\uff0c\u5b9e\u9a8c\u9700\u8981\u4e00\u7cfb\u5217\u6b63\u5e38\u4eba\u7ec6\u80de\u548c\u7ec4\u7ec7\u4f5c\u4e3a\u6d4b\u8bd5\u9776\u6807\u3002\u4e00\u4e9b\u7814\u7a76\u56e2\u961f\u4f7f\u7528\u4eba\u6e90\u539f\u4ee3\u7ec6\u80de\u7cfb\uff0c\u800c\u53e6\u4e00\u4e9b\u5219\u76f4\u63a5\u4ece\u4f9b\u4f53\u83b7\u53d6\u539f\u4ee3\u7ec6\u80de\u548c\u7ec4\u7ec7\u79fb\u690d\u7269\u8fdb\u884c\u6d4b\u8bd5\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u975e\u7279\u5f02\u6027\u6bd2\u6027\u8f83\u96be\u9884\u6d4b\uff0c\u4e14\u5728TCR\u7597\u6cd5\u4e2d\u66f4\u4e3a\u5e38\u89c1\u3002\u5176\u539f\u56e0\u53ef\u80fd\u5305\u62ec\uff1a(1) \u57fa\u56e0\/\u86cb\u767d\u5171\u4eab\u5e8f\u5217\u7684\u5b58\u5728\uff0c\u8fd9\u4e9b\u5e8f\u5217\u53ef\u4ee5\u5728MHC\u80cc\u666f\u4e0b\u4ee5\u7c7b\u4f3c\u80bf\u7624\u6e90\u6027\u8868\u4f4d\u7684\u6784\u8c61\u5448\u73b0\uff1b(2) TCR\u4eb2\u548c\u529b\u8c03\u8c10\uff0c\u5373\u63d0\u9ad8TCR\u5bf9\u7279\u5b9a\u80bd-MHC\u590d\u5408\u7269\u7684\u4eb2\u548c\u529b\uff0c\u53ef\u80fd\u5bfc\u81f4\u5bf9\u6b63\u5e38\u7ec4\u7ec7\u4e2d\u8868\u8fbe\u7684\u5176\u4ed6\u80bd-MHC\u590d\u5408\u7269\u4ea7\u751f\u975e\u7279\u5f02\u6027\u7ed3\u5408\uff0c\u800c\u8fd9\u4e9b\u7ed3\u5408\u901a\u5e38\u5728\u80f8\u817a\u9009\u62e9\u8fc7\u7a0b\u4e2d\u5e94\u88ab\u7b5b\u9664\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u4e00\u4e2a\u5178\u578b\u7684\u4f8b\u5b50\u662fMAGE-A3\u80bd-HLA-A*01\u590d\u5408\u7269\u7684TCR\u4eb2\u548c\u529b\u6210\u719f\uff0c\u540e\u7eed\u5206\u6790\u53d1\u73b0\u60a3\u8005\u6b7b\u4ea1\u7684\u539f\u56e0\u662fTCR\u8bef\u8bc6\u522b\u4e86\u5fc3\u808c\u9ad8\u8868\u8fbe\u7684\u808c\u8089\u86cb\u767dtitin\u3002\u5982\u4eca\uff0c\u9884\u6d4b\u65b0TCR\u4ea4\u53c9\u53cd\u5e94\u6027\u7684\u65b0\u65b9\u6cd5\u5df2\u6210\u4e3a\u4e34\u5e8a\u524d\u5f00\u53d1\u7684\u6807\u51c6\u6b65\u9aa4\uff0c\u8bf8\u5982\u5bf9\u6bd2\u6027\u76f8\u5173\u7ec4\u7ec7\u7684\u4e09\u7ef4\u57f9\u517b\u6a21\u578b\u6d4b\u8bd5\u3001\u80bd\u6392\u5217\u7684\u7cfb\u7edf\u626b\u63cf\uff0c\u4ee5\u53ca\u8ba1\u7b97\u673a\u9884\u6d4b\u7b49\u65b9\u6cd5\uff0c\u80fd\u591f\u5e2e\u52a9\u8bc4\u4f30TCR\u7684\u6f5c\u5728\u4ea4\u53c9\u53cd\u5e94\u6027\u3002\u8fd9\u7c7b\u6b63\u5e38\u7ec6\u80de\/\u7ec4\u7ec7\u6bd2\u6027\u68c0\u6d4b\u65b9\u6cd5\u6b63\u5728\u4e0d\u65ad\u6539\u8fdb\uff0c\u65b0\u7684\u6a21\u578b\u548c\u5b89\u5168\u6280\u672f\u7684\u5f00\u53d1\u8fdb\u5c55\u5c06\u6709\u52a9\u4e8e\u51cf\u5c11\u60a3\u8005\u4e2d\u51fa\u73b0\u672a\u9884\u6599\u7684\u4e0d\u826f\u4e8b\u4ef6\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5728CAR\u548cTCR\u7597\u6cd5\u7684\u5f00\u53d1\u8fc7\u7a0b\u4e2d\uff0c\u4f53\u5185\u6a21\u578b\u6709\u4e00\u5b9a\u4f18\u52bf\u3002\u514d\u75ab\u7f3a\u9677\u5c0f\u9f20\u6a21\u578b\uff08\u5982NOD-SCID-common gamma chain k\/o\uff08NSG\uff09\u6216NOG\u5c0f\u9f20\uff09\u53ef\u7528\u4e8e\u79fb\u690d\u4eba\u7c7b\u80bf\u7624\u548c\u4eba\u7c7bTCR\u6216CAR T\u7ec6\u80de\uff0c\u8fd9\u4e9b\u6a21\u578b\u5177\u6709\u5b8c\u6574\u7684\u5fc3\u8840\u7ba1\u7cfb\u7edf\u548c\u5e7f\u6cdb\u7684\u8840\u7ba1\u7f51\u7edc\uff0c\u80fd\u591f\u5c06T\u7ec6\u80de\u8fd0\u8f93\u81f3\u80bf\u7624\u90e8\u4f4d\u3002\u5c3d\u7ba1\u8fd9\u4e9b\u6a21\u578b\u80fd\u591f\u663e\u793a\u6297\u80bf\u7624\u6548\u679c\u548cT\u7ec6\u80de\u5728\u80bf\u7624\u90e8\u4f4d\u7684\u5b9a\u4f4d\uff0c\u6700\u8fd1\u4e5f\u5728T\u7ec6\u80de\u8017\u7aed\u548c\u68c0\u67e5\u70b9\u963b\u65ad\u65b9\u9762\u663e\u793a\u51fa\u4e00\u5b9a\u7684\u9002\u7528\u6027\uff0c\u4f46\u5b83\u4eec\u4ecd\u5b58\u5728\u5c40\u9650\u6027\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u4e0d\u5e78\u7684\u662f\uff0c\u9f20\u7c7b\u4e0e\u4eba\u7c7b\u4e4b\u95f4\u5171\u4eab\u7684\u80bf\u7624\u9776\u4f4d\u70b9\u6781\u5c11\uff0c\u96be\u4ee5\u63d0\u4f9b\u5173\u4e8e\u5b89\u5168\u6027\u6216\u6b63\u5e38\u7ec4\u7ec7\u6bd2\u6027\u7684\u4fe1\u606f\u3002\u540c\u79cd\u79fb\u690d\u5c0f\u9f20\u6a21\u578b\u5728\u8bc4\u4f30CAR\u7597\u6cd5\u7684\u6709\u6548\u6027\u53ca\u5176\u4e0b\u6e38\u673a\u5236\u65b9\u9762\u6709\u72ec\u7279\u4f18\u52bf\uff0c\u4f46\u8fd9\u4e9b\u6a21\u578b\u5e76\u4e0d\u5b8c\u7f8e\uff1a(1) \u5b83\u4eec\u53ef\u80fd\u9700\u8981\u5177\u6709\u4e0d\u540c\u4eb2\u548c\u529b\u7684\u5355\u514b\u9686\u6297\u4f53\uff1b(2) \u5b83\u4eec\u9700\u8981\u4f7f\u7528\u5c0f\u9f20\u57fa\u56e0\u7f16\u7801\u7684\u8f7d\u4f53\u6784\u5efa\uff0c\u800c\u975e\u4eba\u7c7b\u540c\u6e90\u7269\uff1b(3) \u5c0f\u9f20\u7684\u514d\u75ab\u7cfb\u7edf\u548c\u751f\u7406\u5b66\u4e0e\u4eba\u7c7b\u5dee\u5f02\u663e\u8457\uff0c\u5bfc\u81f4\u6a21\u578b\u4e2d\u7684\u7ed3\u679c\u4e0d\u80fd\u4fdd\u8bc1\u5728\u60a3\u8005\u8eab\u4e0a\u6709\u6548\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u81f3\u4eca\uff0c\u4f7f\u7528\u975e\u4eba\u7075\u957f\u7c7b\u52a8\u7269\uff08NHP\uff09\u6a21\u578b\u5728\u786e\u5b9aCAR\u6216TCR\u7597\u6cd5\u7684\u5b89\u5168\u6027\u548c\u6bd2\u6027\u65b9\u9762\u7684\u6548\u679c\u6709\u9650\uff0c\u4e3b\u8981\u539f\u56e0\u662f\u4eba\u7c7b\u4e0eNHP\u7684\u53ef\u6bd4\u6027\u8f83\u5dee\uff0c\u4e14\u7f3a\u4e4f\u9002\u5408\u7684NHP\u80bf\u7624\u6a21\u578b\u3002\u503c\u5f97\u6ce8\u610f\u7684\u662f\uff0c\u6839\u636e\u7f8e\u56fd\u98df\u54c1\u836f\u54c1\u76d1\u7763\u7ba1\u7406\u5c40\uff08FDA\uff09\u80bf\u7624\u5b66\u7684\u89c4\u5b9a\uff0cI\u671f\u4e34\u5e8a\u8bd5\u9a8c\u7684\u652f\u6301\u76ee\u524d\u5e76\u4e0d\u9700\u8981\u4f9d\u8d56\u52a8\u7269\u6a21\u578b\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n


<\/p>\n<\/section>\n<\/section>\n

\n
\n

42.5 \u57fa\u56e0\u5de5\u7a0bT\u7ec6\u80de\u7597\u6cd5\uff1a\u4e34\u5e8a\u5f00\u53d1<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n

42.5.1 \u5d4c\u5408\u6297\u539f\u53d7\u4f53T\u7ec6\u80de\u6cbb\u7597<\/p>\n<\/section>\n

\n
\n
\n

\u7b2c\u4e00\u4ee3\u5d4c\u5408\u6297\u539f\u53d7\u4f53\uff08CAR\uff09\u5927\u7ea6\u572815\u5e74\u524d\u88ab\u5f15\u5165\u4e34\u5e8a\u8bd5\u9a8c\u3002\u8fd9\u4e9bCAR\u7531\u4e00\u4e2ascFv\u4e0eCD3\u03b6 TCR\u4fe1\u53f7\u94fe\u901a\u8fc7\u77ed\u8de8\u819c\u7ed3\u6784\u57df\u878d\u5408\u800c\u6210\u3002\u8fd9\u79cd\u8bbe\u8ba1\u7684CAR-T\u7ec6\u80de\u80fd\u591f\u5728\u6297\u539f\u8bc6\u522b\u65f6\u8868\u73b0\u51fa\u7ec6\u80de\u6bd2\u6027\u6d3b\u6027\uff0c\u4f46\u7f3a\u4e4f\u6301\u4e45\u6027\u3002\u76ee\u524d\u6b63\u5728\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u6d4b\u8bd5\u7684CAR\u5df2\u8fdb\u5165\u7b2c\u4e8c\u4ee3\u7ed3\u6784\uff0c\u901a\u8fc7\u6dfb\u52a0\u5171\u523a\u6fc0\u4fe1\u53f7\u63d0\u9ad8\u7597\u6548\u3002\u76ee\u524d\u7edd\u5927\u591a\u6570\u4e34\u5e8a\u8bd5\u9a8c\u90fd\u5728\u8bc4\u4f30\u643a\u5e264-1BB\u6216CD28\u57fa\u5e8f\u7684\u7b2c\u4e8c\u4ee3CAR\uff0c\u6b64\u5916\uff0c\u7814\u7a76\u4e5f\u5728\u63a2\u7d22\u5177\u6709\u591a\u4e2a\u5171\u523a\u6fc0\u7ed3\u6784\u57df\u7684\u7b2c\u4e09\u4ee3CAR\uff0c\u4ee5\u53ca\u5f15\u5165OX40\u6216CD27\u7b49\u989d\u5916\u5171\u523a\u6fc0\u7ed3\u6784\u57df\u7684\u7b2c\u56db\u4ee3CAR\u3002\u867d\u7136\u8fd9\u4e9b\u65b0\u4e00\u4ee3\u8bbe\u8ba1\u6b63\u5728\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u6d4b\u8bd5\uff0c\u4f46\u5c1a\u672a\u786e\u5b9a\u5b83\u4eec\u662f\u5426\u80fd\u660e\u663e\u4f18\u4e8e\u7b2c\u4e8c\u4ee3CAR\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

CD19\u5728\u5927\u591a\u6570B\u7ec6\u80de\u767d\u8840\u75c5\u548c\u6dcb\u5df4\u7624\u7684\u8868\u9762\u8868\u8fbe\uff0c\u7531\u4e8e\u5b83\u4ec5\u5728\u6b63\u5e38B\u7ec6\u80de\u4e2d\u8868\u8fbe\uff0c\u800c\u5728\u5176\u4ed6\u6b63\u5e38\u7ec4\u7ec7\u4e2d\u4e0d\u8868\u8fbe\uff0c\u56e0\u6b64\u6210\u4e3a\u8fc7\u7ee7T\u7ec6\u80de\u7597\u6cd5\u4e2d\u6700\u5177\u5438\u5f15\u529b\u7684\u9776\u70b9\u3002\u8bb8\u591a\u5b66\u672f\u4e2d\u5fc3\u6b63\u5728\u5f00\u53d1CD19\u5bfc\u5411\u7684CAR-T\u7ec6\u80de\u4e34\u5e8a\u9879\u76ee\u3002\u521d\u6b65\u7ed3\u679c\u4ee4\u4eba\u632f\u594b\uff0c\u4e0d\u4ec5\u4fc3\u8fdb\u4e86\u591a\u4e2a\u5b66\u672f\u548c\u5236\u836f\u884c\u4e1a\u7684\u5408\u4f5c\u4f19\u4f34\u5173\u7cfb\uff0c\u4e5f\u63a8\u52a8\u4e86\u6ce8\u518c\u7814\u7a76\u7684\u542f\u52a8(Table 42.3<\/span>)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
<\/section>\n<\/section>\n
\n
\n
\n


<\/p>\n<\/section>\n<\/section>\n

\n
\n

Table 42.3<\/span> \u4e34\u5e8a\u6700\u5148\u8fdb\u7684CD19\u9776\u5411CAR-T\u7ec6\u80de\u65b9\u6848\u9009\u62e9<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u7f8e\u56fd\u5bbe\u5915\u6cd5\u5c3c\u4e9a\u5927\u5b66\u7684\u7814\u7a76\u4eba\u5458\u9996\u6b21\u5728\u4e09\u4f8b\u91cd\u5ea6\u9884\u5904\u7406\u7684\u6162\u6027\u6dcb\u5df4\u7ec6\u80de\u767d\u8840\u75c5\uff08CLL\uff09\u60a3\u8005\u4e2d\uff0c\u53d1\u73b0\u4e86\u9776\u5411CD19\u7684CAR-T\u7ec6\u80de\uff08\u542b\u67094-1BB\u5171\u523a\u6fc0\uff0c\u5373CTL019\uff09\u7684\u60ca\u4eba\u4e34\u5e8a\u6d3b\u6027\u3002\u957f\u671f\u968f\u8bbf\u7814\u7a76\u663e\u793a\uff0c14\u540d\u60a3\u8005\u4e2d\u67098\u540d\uff08\u603b\u6709\u6548\u7387 [ORR] \u4e3a57%\uff09\u6709\u53cd\u5e94\uff0c\u5176\u4e2d4\u540d\u60a3\u8005\u8fbe\u5230\u4e86\u5b8c\u5168\u7f13\u89e3\uff08CR\uff09\uff0c\u4e14\u6ca1\u6709\u6700\u5c0f\u6b8b\u7559\u75be\u75c5\uff08MRD\uff09\u7684\u8bc1\u636e\u3002\u4ee4\u4eba\u77a9\u76ee\u7684\u662f\uff0c\u8fd9\u4e9bCAR-T\u7ec6\u80de\u5728\u4f53\u5185\u53ef\u6301\u7eed\u6570\u5e74\uff0c\u4e14\u5728\u672c\u7814\u7a76\u4e2d\uff0c\u672a\u6709CR\u60a3\u8005\u51fa\u73b0\u590d\u53d1\uff0c\u8fdb\u4e00\u6b65\u5c55\u793a\u4e86\u8fd9\u79cd\u7597\u6cd5\u7684\u6cbb\u7597\u6f5c\u529b\u3002\u622a\u81f3\u76ee\u524d\uff0c\u8d85\u8fc745\u4f8b\u590d\u53d1\u6216\u96be\u6cbb\u6027CLL\u60a3\u8005\u5728\u5bbe\u5915\u6cd5\u5c3c\u4e9a\u5927\u5b66\u63a5\u53d7\u4e86\u6cbb\u7597\uff0cORR\u4e3a45%\u3002\u5176\u4ed6\u7814\u7a76\u7ec4\u5728\u8f83\u5c0f\u7684\u60a3\u8005\u961f\u5217\u4e2d\u4e5f\u5c55\u793a\u4e86\u7c7b\u4f3c\u7684CLL\u6d3b\u6027\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
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\u591a\u4e2a\u7814\u7a76\u5c0f\u7ec4\u8fd8\u62a5\u9053\u4e86\u4f7f\u7528\u4e0d\u540cCAR-T\u7ec6\u80de\u8bbe\u8ba1\u6cbb\u7597\u590d\u53d1\/\u96be\u6cbb\u6027\u6025\u6027\u6dcb\u5df4\u7ec6\u80de\u767d\u8840\u75c5\uff08ALL\uff09\u7684\u513f\u7ae5\u548c\u6210\u4eba\u60a3\u8005\uff0c\u83b7\u5f97\u4e86\u9ad8CR\u7387\u3002\u8d39\u57ce\u513f\u7ae5\u533b\u9662\u548c\u5bbe\u5915\u6cd5\u5c3c\u4e9a\u5927\u5b66\u5728\u4e00\u9879\u7814\u7a76\u4e2d\u62a5\u9053\u4e8630\u4f8bALL\u60a3\u8005\uff0825\u4f8b\u513f\u7ae5\uff0c5\u4f8b\u6210\u4eba\uff09\u63a5\u53d7CTL019\u6cbb\u7597\u7684\u7ed3\u679c\u300227\u4f8b\u60a3\u8005\uff0890%\uff09\u8fbe\u5230\u4e86CR\uff0c6\u4e2a\u6708\u7684\u751f\u5b58\u7387\u4e3a78%\uff0c\u5e76\u4e14\u5728\u67d0\u4e9b\u60a3\u8005\u4e2d\u89c2\u5bdf\u5230\u4e86\u957f\u8fbe24\u4e2a\u6708\u7684\u6301\u4e45\u7f13\u89e3\uff0c\u8fd9\u4e9b\u7f13\u89e3\u4e0e\u6301\u7eed\u5b58\u5728\u7684CAR-T\u7ec6\u80de\u76f8\u5173\u3002\u7f8e\u56fd\u56fd\u5bb6\u764c\u75c7\u7814\u7a76\u6240\u4f7f\u752819-28z CAR-T\u7ec6\u80de\u6cbb\u7597\u4e8645\u540d\u513f\u7ae5\u548c\u5e74\u8f7b\u4eba\uff0c\u62a5\u544a\u7684CR\u7387\u4e3a60%\u3002\u5728\u5206\u6790\u65f6\uff0c\u6240\u6709\u60a3\u8005\u4ecd\u7136\u5b58\u6d3b\uff0c89%\u4fdd\u6301\u65e0\u75c5\u72b6\u6001\uff08\u6301\u7eed\u65f6\u95f45-28\u4e2a\u6708\uff09\u3002\u7eaa\u5ff5\u65af\u9686\u51ef\u7279\u7433\u764c\u75c7\u4e2d\u5fc3\u62a5\u544a\u4e8645\u540d\u590d\u53d1\u6027ALL\u6210\u5e74\u60a3\u8005\u63a5\u53d7JCAR015\u6cbb\u7597\u7684\u7ed3\u679c\uff0cJCAR015\u662f\u4e00\u79cd\u542b\u6709CD28\u5171\u523a\u6fc0\u5206\u5b50\u7684\u9776\u5411CD19\u7684CAR\u3002\u5c3d\u7ba1CAR-T\u7ec6\u80de\u7684\u6301\u7eed\u65f6\u95f4\u4ec5\u4e3a\u51e0\u4e2a\u6708\uff0c\u4f4682%\u7684\u60a3\u8005\u8fbe\u5230\u4e86CR\u3002Fred Hutchinson\u764c\u75c7\u7814\u7a76\u4e2d\u5fc3\u7684\u7814\u7a76\u663e\u793a\uff0c29\u4f8b\u590d\u53d1ALL\u60a3\u8005\u4e2d\u670927\u4f8b\uff0893%\uff09\u5728\u4ee5CD8+<\/p>\n

+ 1:1\u6bd4\u4f8b\u8f93\u6ce8\u542b\u67094-1BB\u7684CAR-T\u7ec6\u80de\u540e\u8fbe\u5230\u4e86CR\uff0c\u5176\u4e2d25\u4f8b\uff0886%\uff09\u65e0MRD\u7684\u8bc1\u636e\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
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CD19\u5bfc\u5411\u7684CAR-T\u7ec6\u80de\u7597\u6cd5\u5728\u91cd\u5ea6\u9884\u5904\u7406\u7684\u975e\u970d\u5947\u91d1\u6dcb\u5df4\u7624\uff08NHL\uff09\u60a3\u8005\u4e2d\u4e5f\u5c55\u73b0\u4e86\u826f\u597d\u7684\u6d3b\u6027\u3002\u5728\u7f8e\u56fd\u56fd\u5bb6\u764c\u75c7\u7814\u7a76\u6240\uff0c9\u4f8b\u590d\u53d1\/\u96be\u6cbb\u6027\u5f25\u6f2b\u6027\u5927B\u7ec6\u80de\u6dcb\u5df4\u7624\uff08DLBCL\uff09\u60a3\u8005\u7684ORR\u4e3a67%\uff0c\u800c\u5728\u5bbe\u5915\u6cd5\u5c3c\u4e9a\u5927\u5b66\uff0c15\u4f8bDLBCL\u60a3\u8005\u7684ORR\u4e3a47%\uff0c8\u4f8b\u53ef\u8bc4\u4f30\u7684\u590d\u53d1\/\u96be\u6cbb\u6027\u6ee4\u6ce1\u6027\u6dcb\u5df4\u7624\u60a3\u8005\u7684ORR\u4e3a73%\u3002\u5728\u8fd9\u9879\u7814\u7a76\u4e2d\uff0c\u672a\u8fbe\u5230CR\u7684\u60a3\u8005\u6700\u7ec8\u51fa\u73b0\u4e86\u590d\u53d1\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u7531Kite\u516c\u53f8\u8d5e\u52a9\u7684\u591a\u4e2d\u5fc3\u5173\u952e\u7814\u7a76ZUMA-1\u6d4b\u8bd5\u4e86\u542b\u6709CD28\u5171\u523a\u6fc0\u7ed3\u6784\u57df\u7684CAR-T\u7ec6\u80deKTE-C19\uff08axicabtagene ciloleucel, Axi-cel\uff09\uff0c\u5176\u7ed3\u679c\u5df2\u7ecf\u62a5\u9053\u3002\u7814\u7a76\u4e2d\u5171\u6709101\u4f8b\u4fb5\u88ad\u6027\u975e\u970d\u5947\u91d1\u6dcb\u5df4\u7624\uff08NHL\uff09\u60a3\u8005\uff08\u5305\u62ec77\u4f8b\u5f25\u6f2b\u6027\u5927B\u7ec6\u80de\u6dcb\u5df4\u7624\uff08DLBCL\uff09\u548c24\u4f8b\u539f\u53d1\u6027\u7eb5\u9694B\u7ec6\u80de\u6dcb\u5df4\u7624\u6216\u8f6c\u5316\u578b\u6ee4\u6ce1\u6027\u6dcb\u5df4\u7624\uff09\u63a5\u53d7\u4e86\u6c1f\u8fbe\u62c9\u6ee8\u548c\u73af\u78f7\u9170\u80fa\u8054\u5408\u7684\u6dcb\u5df4\u7ec6\u80de\u6e05\u9664\u6cbb\u7597\uff0c\u968f\u540e\u4ee52 \u00d7 10\u2076\u7ec6\u80de\/kg\u7684\u5242\u91cf\u8f93\u6ce8Axi-cel\u3002\u7814\u7a76\u663e\u793a\uff0cORR\u4e3a82%\uff0c\u5176\u4e2dCR\u7387\u4e3a54%\uff0c6\u4e2a\u6708\u7684\u603b\u751f\u5b58\u7387\uff08OS\uff09\u4e3a80%\u3002\u622a\u81f3\u6570\u636e\u622a\u6b62\u65f6\uff0c44%\u7684\u60a3\u8005\u4ecd\u5904\u4e8e\u7f13\u89e3\u671f\u3002ZUMA-1\u7684\u7814\u7a76\u7ed3\u679c\u5df2\u63d0\u4ea4\u7ed9\u7f8e\u56fd\u98df\u54c1\u836f\u54c1\u76d1\u7763\u7ba1\u7406\u5c40\uff08FDA\uff09\uff0c\u4ee5\u652f\u6301Axi-cel\u7684\u751f\u7269\u5236\u54c1\u8bb8\u53ef\u8bc1\u7533\u8bf7\uff0c\u7528\u4e8e\u6cbb\u7597\u590d\u53d1\u6216\u96be\u6cbb\u6027\u4fb5\u88ad\u6027NHL\u4e14\u4e0d\u9002\u5408\u79fb\u690d\u7684\u60a3\u8005\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u603b\u4f53\u6765\u770b\uff0c\u8fd9\u4e9b\u7ed3\u679c\u8868\u660eCAR-T\u7ec6\u80de\u7597\u6cd5\u5728CD19+ B\u7ec6\u80de\u6076\u6027\u80bf\u7624\u4e2d\u7684\u6210\u529f\u5e94\u7528\uff0c\u4f46\u4e5f\u51f8\u663e\u4e86\u5176\u6f5c\u5728\u7684\u81f4\u547d\u6bd2\u6027\u98ce\u9669\u3002\u5c3d\u7ba1\u5982\u6b64\uff0c\u98ce\u9669\/\u6536\u76ca\u6bd4\u5f3a\u70c8\u652f\u6301\u5728\u6076\u6027\u80bf\u7624\uff08\u5982\u590d\u53d1\/\u96be\u6cbb\u6027ALL\u6216DLBCL\uff09\u4e2d\u4f7f\u7528CAR-T\u7ec6\u80de\uff0c\u8fd9\u4e9b\u80bf\u7624\u8feb\u5207\u9700\u8981\u6709\u6548\u7684\u6cbb\u7597\u624b\u6bb5\u3002\u9884\u8ba1CD19\u9776\u5411CAR-T\u7ec6\u80de\u7684\u4e34\u5e8a\u8bd5\u9a8c\u7ed3\u679c\u53ef\u80fd\u57282017\u5e74\u9996\u6b21\u83b7\u5f97\u76d1\u7ba1\u673a\u6784\u6279\u51c6\uff0c\u7528\u4e8eALL\u548cDLBCL\u60a3\u8005\u7684\u57fa\u56e0\u5de5\u7a0b\u8fc7\u7ee7\u6027T\u7ec6\u80de\u7597\u6cd5\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u6b64\u5916\uff0c\u4e00\u7cfb\u5217\u4e34\u5e8a\u524d\u548c\u65e9\u671f\u4e34\u5e8a\u7ed3\u679c\u8868\u660e\uff0c\u9776\u5411\u591a\u53d1\u6027\u9aa8\u9ad3\u7624\u4e2d\u8868\u8fbe\u7684B\u7ec6\u80de\u6210\u719f\u6297\u539f\uff08BCMA\uff09\u7684CAR-T\u7ec6\u80de\u6709\u671b\u6210\u4e3a\u8be5\u6280\u672f\u7684\u4e0b\u4e00\u4e2a\u4e34\u5e8a\u5e94\u7528\u7a81\u7834\u3002\u591a\u4e2a\u56e2\u4f53\uff0c\u5305\u62ec\u5357\u4eac\u8054\u60f3\u751f\u7269\u6280\u672f\u6709\u9650\u516c\u53f8\u3001Kite\u3001bluebird\u548c\u8bfa\u534e\uff0c\u6b63\u5728\u5f00\u53d1\u9776\u5411BCMA\u7684CAR-T\u7ec6\u80de\u3002\u540c\u6837\uff0c\u9488\u5bf9\u5b9e\u4f53\u764c\u4e2d\u8868\u8fbe\u7684\u591a\u79cd\u6297\u539f\u7684CAR-T\u7ec6\u80de\u7597\u6cd5\u4e5f\u5728\u8fdb\u884c\u4e2d(Table 42.2<\/span>\u548cFig 42.1<\/span>)\u3002\u5728\u95f4\u76ae\u7d20\uff08\u7528\u4e8e\u6cbb\u7597\u95f4\u76ae\u7624\u3001\u80f0\u817a\u764c\u3001\u5375\u5de2\u764c\uff09\u548cEGFRvIII\uff08\u7528\u4e8e\u6cbb\u7597\u80f6\u8d28\u6bcd\u7ec6\u80de\u7624\uff09\u7684\u65e9\u671f\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\uff0c\u5df2\u786e\u8ba4\u4e86\u8be5\u6280\u672f\u7684\u5b89\u5168\u6027\u3002\u5c3d\u7ba1\u4e0eB\u7ec6\u80de\u6076\u6027\u80bf\u7624\u4e2d\u7684\u7597\u6548\u76f8\u6bd4\uff0c\u73b0\u6709\u7684\u5b9e\u4f53\u7624\u7597\u6548\u7ed3\u679c\u5c1a\u4e0d\u7406\u60f3\uff0c\u4f46\u7531\u4e8e\u5f53\u524d\u4e34\u5e8a\u8bd5\u9a8c\u7684\u60a3\u8005\u6570\u91cf\u6709\u9650\uff0c\u5c1a\u65e0\u6cd5\u5bf9CAR-T\u7ec6\u80de\u7597\u6cd5\u5728\u5b9e\u4f53\u7624\u4e2d\u7684\u6f5c\u529b\u4f5c\u51fa\u660e\u786e\u7ed3\u8bba\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n

42.5.2 T\u7ec6\u80de\u53d7\u4f53\u8f6c\u5bfcT\u7ec6\u80de<\/p>\n<\/section>\n

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\u5982\u524d\u6240\u8ff0\uff0c\u5341\u591a\u5e74\u524d\uff0c\u7f8e\u56fd\u56fd\u5bb6\u764c\u75c7\u7814\u7a76\u6240\uff08NCI\uff09\u7684\u7814\u7a76\u4eba\u5458\u8bc1\u5b9e\uff0c\u4ece\u81ea\u4f53\u65b0\u9c9c\u80bf\u7624\u6837\u672c\u4e2d\u63d0\u53d6\u5e76\u4f53\u5916\u6269\u589e\u7684\u9ed1\u8272\u7d20\u7624\u53cd\u5e94\u6027\u80bf\u7624\u6d78\u6da6\u6dcb\u5df4\u7ec6\u80de\uff08TILs\uff09\u8fc7\u7ee7\u79fb\u690d\uff0c\u80fd\u591f\u572849-72%\u7684\u8f6c\u79fb\u6027\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\u8bf1\u5bfc\u80bf\u7624\u6d88\u9000\u3002\u7136\u800c\uff0c\u8fd9\u79cd\u65b9\u6cd5\u4ec5\u9002\u7528\u4e8e\u4e00\u534a\u80fd\u4ea7\u751fTIL\u7684\u9ed1\u8272\u7d20\u7624\u60a3\u8005\uff0c\u5728\u5176\u4ed6\u6076\u6027\u80bf\u7624\u4e2d\u7684\u6210\u529f\u7387\u975e\u5e38\u6709\u9650\u3002\u8fd9\u4e00\u5c40\u9650\u6027\u63a8\u52a8\u4e86\u7ec6\u80de\u8f6c\u79fb\u7814\u7a76\u7684\u8fdb\u4e00\u6b65\u53d1\u5c55\uff0c\u5728\u8fd9\u4e9b\u7814\u7a76\u4e2d\uff0cT\u7ec6\u80de\u88ab\u57fa\u56e0\u5de5\u7a0b\u6539\u9020\uff0c\u4ee5\u8868\u8fbe\u9488\u5bf9\u591a\u79cd\u4eba\u7c7b\u764c\u75c7\u6297\u539f\u7684TCR\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\n
\n

\u4e00\u9879\u4e34\u5e8a\u8bd5\u9a8c\u9996\u6b21\u63d0\u4f9b\u4e86\u57fa\u4e8eTCR\u57fa\u56e0\u6cbb\u7597\u80fd\u591f\u5728\u764c\u75c7\u60a3\u8005\u4e2d\u8bf1\u5bfc\u6df1\u523b\u4e14\u6301\u4e45\u53cd\u5e94\u7684\u65e9\u671f\u8bc1\u636e\u3002\u5728\u8be5\u8bd5\u9a8c\u4e2d\uff0c13\u540d\u60a3\u8005\u4e2d\u67092\u540d\u5728\u63a5\u53d7\u8fc7\u7ee7\u6027\u8f6c\u79fb\u7684\u8868\u8fbeMART-1\u53cd\u5e94\u6027TCR\u7684\u81ea\u4f53T\u7ec6\u80de\u540e\uff0c\u51fa\u73b0\u4e86\u80bf\u7624\u6d88\u9000\u3002\u5728\u968f\u540e\u7684\u7814\u7a76\u4e2d\uff0c\u4f7f\u7528\u4e86\u66f4\u9ad8\u4eb2\u548c\u529b\u7684MART-1 TCR\uff0c\u5176\u4e2d20\u540d\u60a3\u8005\u4e2d\u67096\u540d\uff0830%\uff09\u548c16\u540d\u60a3\u8005\u4e2d\u67093\u540d\uff0819%\uff09\u63a5\u53d7\u4e86\u9f20\u6e90\u6027\u6297\u4ebagp100\u9ad8\u4eb2\u548c\u529bTCR\u6cbb\u7597\u3002\u4e0d\u5e78\u7684\u662f\uff0c\u6cbb\u7597\u8fc7\u7a0b\u4e2d\u51fa\u73b0\u4e86\u4e25\u91cd\u7684\u9776\u5916\u80bf\u7624\u6bd2\u6027\uff0c\u4e3b\u8981\u5f71\u54cd\u60a3\u8005\u76ae\u80a4\u3001\u773c\u775b\u548c\u8033\u6735\u4e2d\u7684\u6b63\u5e38\u9ed1\u8272\u7d20\u7ec6\u80de\uff0c\u8fd9\u7a81\u51fa\u663e\u793a\u4e86\u9776\u5411\u51e0\u4e4e\u5b8c\u5168\u7f3a\u5931\u4e8e\u6b63\u5e38\u7ec4\u7ec7\u7684\u6297\u539f\u7684\u5fc5\u8981\u6027\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u6b63\u5982\u672c\u7ae0\u524d\u9762\u63d0\u5230\u7684\uff0c\u4f7f\u7528MAGE-A3\u53cd\u5e94\u6027TCR\u8f6c\u5bfc\u7684T\u7ec6\u80de\u8fc7\u7ee7\u8f6c\u79fb\uff0c\u56e0\u4e24\u79cd\u4e0d\u540cTCR\u7684\u9776\u4ea4\u53c9\u53cd\u5e94\u6027\u5bfc\u81f4\u4e86\u610f\u5916\u6b7b\u4ea1\u3002\u5982\u4eca\uff0c\u5df2\u7ecf\u53ef\u4ee5\u901a\u8fc7\u4f53\u5916\u5b9e\u9a8c\u548c\u8ba1\u7b97\u673a\u6a21\u62df\u65b9\u6cd5\u9884\u6d4b\u65b0\u578bTCR\u7ed3\u6784\u7684\u4ea4\u53c9\u53cd\u5e94\u6027\uff0c\u8fd9\u5c06\u5927\u5927\u63d0\u9ad8\u65b0\u578bTCR\u5de5\u7a0b\u4ea7\u54c1\u7684\u60a3\u8005\u5b89\u5168\u6027\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5230\u76ee\u524d\u4e3a\u6b62\uff0c\u53ea\u6709\u6709\u9650\u7684\u7814\u7a76\u63a2\u7d22\u4e86TCR T\u7ec6\u80de\u6280\u672f\uff0c\u5e76\u663e\u793a\u51fa\u4e00\u81f4\u7684\u4e34\u5e8a\u6d3b\u6027\u3002\u5229\u7528TCR\u5de5\u7a0b\u5916\u5468T\u7ec6\u80de\u9776\u5411\u764c\u75c7\u6297\u539f\u7ebd\u7ea6\u98df\u7ba1\u9cde\u72b6\u7ec6\u80de\u764c1\uff08NY-ESO-1\uff09\u7684\u7814\u7a76\uff0c\u4ea7\u751f\u4e86\u6700\u4e3a\u6709\u524d\u666f\u7684\u6570\u636e\u3002\u56e0\u6b64\uff0c\u8fd9\u7c7b\u8bd5\u9a8c\u9700\u8981\u7279\u522b\u5173\u6ce8\u548c\u8fdb\u4e00\u6b65\u7814\u7a76\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n

42.5.2.1 \u7784\u51c6NY-ESO-1<\/p>\n<\/section>\n

\n
\n
\n

NY-ESO-1\u662f\u4e00\u79cd\u764c\u80da\u6297\u539f\uff08CGA\uff09\uff0c\u5728\u591a\u79cd\u80bf\u7624\u4e2d\u8868\u8fbe\uff0c\u5305\u62ec10-50%\u7684\u8f6c\u79fb\u6027\u9ed1\u8272\u7d20\u7624\u3001\u80ba\u764c\u3001\u4e73\u817a\u764c\u548c\u5375\u5de2\u764c\uff0c\u4ee5\u53ca70-80%\u7684\u6ed1\u819c\u8089\u7624\u3002NCI\u7814\u7a76\u4eba\u5458\u4e8e2011\u5e74\u9996\u6b21\u53d1\u8868\u4e86\u4f7f\u7528\u03b3-\u9006\u8f6c\u5f55\u75c5\u6bd2\u5411\u81ea\u4f53T\u7ec6\u80de\u9012\u9001\u9488\u5bf9HLA-A*02\u9650\u5236\u6027NY-ESO-1\u4e5d\u80bd\uff08\u6b8b\u57fa157-165\uff09\u7684\u9ad8\u4eb2\u548c\u529bTCR\u7684\u4e34\u5e8a\u7814\u7a76\u7ed3\u679c\u300217\u540d\u60a3\u8005\uff086\u4f8b\u6ed1\u819c\u8089\u7624\u548c11\u4f8b\u9ed1\u8272\u7d20\u7624\uff09\u643a\u5e26NY-ESO-1\u6297\u539f\u5f3a\u8868\u8fbe\u7684\u80bf\u7624\uff082-4+\uff0c>50%\u7684\u7ec6\u80de\uff09\u3002\u6cbb\u7597\u65b9\u6848\u5305\u62ec\u6dcb\u5df4\u7ec6\u80de\u6d88\u8017\u6027\u5316\u7597\uff08\u73af\u78f7\u9170\u80fa60 mg\/kg\/d\uff0c\u51712\u5929\uff0c\u6c1f\u8fbe\u62c9\u6ee825 mg\/m\u00b2\/d\uff0c\u51715\u5929\uff09\uff0c\u968f\u540e\u8f93\u6ce8NY-ESO-1 TCR\u8f6c\u5bfcT\u7ec6\u80de\uff08\u4e2d\u4f4d\u65705 \u00d7 10\u00b9\u2070\uff0c\u8303\u56f41.6 ~ 130 \u00d7 10\u2079\uff09\uff0c\u5e76\u8f85\u4ee5\u5168\u8eabIL-2\u6cbb\u7597\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u7814\u7a76\u7ed3\u679c\u663e\u793a\uff0c9\u540d\u60a3\u8005\u6709\u53cd\u5e94\uff0c\u5176\u4e2d2\u540d\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u8fbe\u5230\u6301\u7eed\u8d85\u8fc71\u5e74\u7684\u5b8c\u5168\u7f13\u89e3\uff08CR\uff09\uff0c1\u540d\u6ed1\u819c\u8089\u7624\u60a3\u8005\u8fbe\u5230\u4e86\u6301\u7eed18\u4e2a\u6708\u7684\u90e8\u5206\u7f13\u89e3\uff08PR\uff09\u3002\u6700\u8fd1\u7684\u7814\u7a76\u66f4\u65b0\u5305\u62ec\u53e6\u591621\u540d\u60a3\u8005\u7684\u6570\u636e\uff0812\u4f8b\u6ed1\u819c\u8089\u7624\uff0c9\u4f8b\u9ed1\u8272\u7d20\u7624\uff09\u3002\u6ed1\u819c\u8089\u7624\u7684ORR\u4e3a61%\uff0c\u4f30\u8ba1\u76843\u5e74\u751f\u5b58\u7387\u548c5\u5e74\u751f\u5b58\u7387\u5206\u522b\u4e3a38%\u548c14%\u3002\u5728\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\uff0cORR\u4e3a55%\uff0c\u4f30\u8ba1\u76843\u5e74\u548c5\u5e74\u751f\u5b58\u7387\u5747\u4e3a33%\u3002\u7814\u7a76\u4e2d\u89c2\u5bdf\u5230\u7684\u6bd2\u6027\u4e3b\u8981\u662f\u4e0e\u6dcb\u5df4\u6d88\u8017\u65b9\u6848\u548cIL-2\u6cbb\u7597\u76f8\u5173\u7684\u9884\u671f\u53cd\u5e94\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u8fd9\u4e9b\u7ed3\u679c\u9a8c\u8bc1\u4e86NY-ESO-1\u4f5c\u4e3a\u8fc7\u7ee7\u6027T\u7ec6\u80de\u514d\u75ab\u6cbb\u7597\u4e2d\u4e00\u4e2a\u6709\u524d\u666f\u7684\u764c\u75c7\u6297\u539f\u3002Adaptimmune Therapeutics\uff0c\u4e00\u5bb6\u751f\u7269\u6280\u672f\u516c\u53f8\uff0c\u5229\u7528\u5176\u4e13\u6709\u7684SPEAR\u00ae\uff08\u7279\u5f02\u6027\u80bd\u5de5\u7a0b\u4eb2\u548c\u53d7\u4f53\uff09T\u7ec6\u80de\u5de5\u7a0b\u5e73\u53f0\uff0c\u5df2\u5728HLA-A*02\u9633\u6027\u7684NY-ESO-1\u8868\u8fbe\u80bf\u7624\u60a3\u8005\u4e2d\u5f00\u5c55\u4e86\u516d\u9879\u4e34\u5e8a\u7814\u7a76\u3002\u622a\u81f32016\u5e741\u6708\uff0c\u5df2\u670953\u540d\u60a3\u8005\u63a5\u53d7\u4e86NY-ESO-1c259SPEAR\u00ae\u6cbb\u7597\uff0c\u5176\u4e2d27\u4f8b\u4e3a\u591a\u53d1\u6027\u9aa8\u9ad3\u7624\uff0c26\u4f8b\u4e3a\u5404\u79cd\u5b9e\u4f53\u7624\uff0c\u5305\u62ec\u6ed1\u819c\u8089\u7624\u3001\u9ed1\u8272\u7d20\u7624\u3001\u5375\u5de2\u764c\u548cNSCLC\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u8fc4\u4eca\u4e3a\u6b62\uff0c\u5728\u5b9e\u4f53\u7624\u7814\u7a76\u4e2d\uff0c\u6ed1\u819c\u8089\u7624\u7684\u6570\u636e\u6700\u591a\u3002\u572812\u4f8b\u4e0d\u53ef\u5207\u9664\u3001\u8f6c\u79fb\u6027\u6216\u590d\u53d1\u6027\u6ed1\u819c\u8089\u7624\u60a3\u8005\u4e2d\uff0c6\u4f8b\u8fbe\u5230\u4e86\u5ba2\u89c2\u7f13\u89e3\uff08ORR\u4e3a50%\uff09\u3002\u5728\u5375\u5de2\u764c\u548c\u9ed1\u8272\u7d20\u7624\u7684\u7814\u7a76\u4e2d\uff0c\u5206\u522b\u67096\u540d\u548c4\u540d\u60a3\u8005\u63a5\u53d7\u4e86\u6cbb\u7597\uff0c\u4f46\u76ee\u524d\u5c1a\u672a\u89c2\u5bdf\u5230\u4efb\u4f55\u76ee\u6807\u7f13\u89e3\u3002\u503c\u5f97\u6ce8\u610f\u7684\u662f\uff0c\u8fd9\u4e24\u79cd\u9002\u5e94\u75c7\u7684\u6dcb\u5df4\u7ec6\u80de\u6d88\u8017\u65b9\u6848\u5b8c\u5168\u7531\u73af\u78f7\u9170\u80fa\u7ec4\u6210\uff08\u672a\u4f7f\u7528\u6c1f\u8fbe\u62c9\u6ee8\uff09\uff0c\u8fd9\u53ef\u80fd\u90e8\u5206\u89e3\u91ca\u4e86\u7f3a\u4e4f\u5ba2\u89c2\u53cd\u5e94\u7684\u539f\u56e0\u3002\u672a\u6765\u7684\u8bd5\u9a8c\u5c06\u91c7\u7528\u6807\u51c6\u7684NY-ESO-1\u7b5b\u67e5\u548c\u542b\u6c1f\u8fbe\u62c9\u6ee8\u7684\u6dcb\u5df4\u6d88\u8017\u65b9\u6848\u3002\u53e6\u4e00\u4e2a\u91cd\u8981\u53d1\u73b0\u662f\uff0cNY-ESO-1c259SPEAR\u2122T\u7ec6\u80de\u5728\u8f93\u6ce8\u540e3\u5e74\u4ee5\u4e0a\u4ecd\u53ef\u6301\u7eed\u5b58\u5728\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u5bbe\u5915\u6cd5\u5c3c\u4e9a\u5927\u5b66\u7684\u7814\u7a76\u4eba\u5458\u5c06TCR NY-ESO-1\u7684\u5e94\u7528\u6269\u5c55\u5230\u591a\u53d1\u6027\u9aa8\u9ad3\u7624\uff0c\u5229\u7528\u6162\u75c5\u6bd2\u5e73\u53f0\u4f7fT\u7ec6\u80de\u8868\u8fbe\u8bc6\u522bNY-ESO-1\u7684TCR\u3002\u5728\u8fd9\u9879\u7814\u7a76\u4e2d\uff0c20\u4f8bNY-ESO-1\u9633\u6027\u7684\u591a\u53d1\u6027\u9aa8\u9ad3\u7624\u60a3\u8005\u5728\u63a5\u53d7\u81ea\u4f53\u5e72\u7ec6\u80de\u79fb\u690d\uff08SCT\uff09\u4e24\u5929\u540e\uff0c\u63a5\u53d7\u4e86\u57fa\u56e0\u5de5\u7a0bT\u7ec6\u80de\u6cbb\u7597\u3002\u7ed3\u679c\u663e\u793a\uff0cNY-ESO-1 TCR\u5de5\u7a0bT\u7ec6\u80de\u662f\u5b89\u5168\u7684\uff0c\u80fd\u591f\u6301\u7eed\u8f93\u9001\u5230\u9aa8\u9ad3\u4e2d\uff0c\u5e76\u4e14\u8868\u73b0\u51fa\u4e0e\u591a\u53d1\u6027\u9aa8\u9ad3\u7624\u4e34\u5e8a\u6d3b\u6027\u76f8\u5173\u7684\u5ef6\u957f\u6301\u4e45\u6027\u3002\u60a3\u8005\u7684\u4e2d\u4f4d\u65e0\u8fdb\u5c55\u751f\u5b58\u671f\uff08PFS\uff09\u4e3a19.1\u4e2a\u6708\uff0c\u8fd9\u8868\u660e\u8be5\u65b9\u6cd5\u5728\u590d\u53d1\/\u96be\u6cbb\u6027\u591a\u53d1\u6027\u9aa8\u9ad3\u7624\u60a3\u8005\u4e2d\u5177\u6709\u6f5c\u5728\u7597\u6548\u3002\u672a\u6765\uff0c\u5982\u4f55\u51c6\u786e\u8bc4\u4f30NY-ESO-1 TCR T\u7ec6\u80de\u7684\u6d3b\u6027\uff0c\u800c\u4e0d\u53d7\u81ea\u4f53SCT\u7684\u5e72\u6270\uff0c\u5c06\u662f\u4e00\u4e2a\u91cd\u8981\u7684\u7814\u7a76\u65b9\u5411\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n

\u6700\u8fd1\u7684\u7814\u7a76\u8fd8\u8868\u660e\uff0cNY-ESO-1\u5de5\u7a0bT\u7ec6\u80de\u5728\u5f02\u79cd\u79fb\u690d\u5c0f\u9f20\u4e2d\u5bf9\u64ad\u6563\u6027\u795e\u7ecf\u6bcd\u7ec6\u80de\u7624\u663e\u793a\u51fa\u7597\u6548\u3002\u8fd9\u4e9b\u975e\u4e34\u5e8a\u6570\u636e\u652f\u6301\u4e86NY-ESO-1\u4f5c\u4e3a\u4e00\u4e2a\u5408\u9002\u9776\u70b9\u7684\u6f5c\u529b\uff0c\u9664\u4e86\u6ed1\u819c\u8089\u7624\u3001\u6076\u6027\u9ed1\u8272\u7d20\u7624\u548c\u591a\u53d1\u6027\u9aa8\u9ad3\u7624\u4e4b\u5916\uff0c\u8fd8\u53ef\u80fd\u5728\u5176\u4ed6\u80bf\u7624\u7c7b\u578b\u4e2d\u53d1\u6325\u4f5c\u7528\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n

42.5.2.2 \u5176\u4ed6\u4e34\u5e8aTCR\u9776\u70b9<\/p>\n<\/section>\n

\n
\n
\n

\u5c3d\u7ba1TCR T\u7ec6\u80de\u5bf9NY-ESO-1\u9633\u6027\u80bf\u7624\u7684\u6cbb\u7597\u6d3b\u6027\u8f83\u4f4e\uff0c\u5e76\u4e14\u7531\u4e8eTCR T\u7ec6\u80de\u7684\u6709\u9650\u6301\u4e45\u6027\u53d7\u5230\u963b\u788d\uff0c\u8fd9\u53ef\u80fd\u9650\u5236\u4e86\u6301\u7eed\u53cd\u5e94\u7684\u5b9e\u73b0\uff0c\u5e76\u5bfc\u81f4\u7531\u4e8e\u7ec4\u7ec7\u8d1f\u8377\u800c\u4ea7\u751f\u4e0d\u826f\u6bd2\u6027\u3002\u76ee\u524d\uff0c\u591a\u4e2a\u5728\u6b63\u5e38\u7ec4\u7ec7\u4e2d\u4f4e\u6c34\u5e73\u8868\u8fbe\u7684\u764c\u75c7\u76f8\u5173\u6297\u539f\uff08\u5982CG\u6297\u539f\u3001CEA\u548cHer2\uff09\u6b63\u6210\u4e3aTCR\u5de5\u7a0bT\u7ec6\u80de\u7684\u9776\u5411\u76ee\u6807(Table 42.1<\/span>)\u3002\u672a\u67652-3\u5e74\u5185\uff0c\u968f\u7740\u9488\u5bf9\u4e0d\u540c\u6297\u539f\u7684TCR\u5de5\u7a0bT\u7ec6\u80de\u8fdb\u5165\u4e34\u5e8a\u7814\u7a76\uff0c\u66f4\u591a\u7684\u4e34\u5e8a\u6570\u636e\u5c06\u5e2e\u52a9\u6211\u4eec\u786e\u5b9a\u6cbb\u7597\u764c\u75c7\u60a3\u8005\u7684\u6700\u4f73\u9776\u70b9\u548cTCR\u8bbe\u8ba1(Table 42.4<\/span>)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
<\/section>\n<\/section>\n
\n
\n
\n


<\/p>\n<\/section>\n<\/section>\n

\n
\n

Table 42.4 <\/span>\u4e34\u5e8aTCR T\u7ec6\u80de\u4ea7\u54c1<\/span><\/p>\n

\u6765\u6e90: clinicaltrials.gov<\/span><\/p>\n

\u9664\u975e\u7279\u522b\u8bf4\u660e\uff0c\u6240\u6709\u6b63\u5728\u8fdb\u884c\u7684TCR T\u7ec6\u80de\u4e34\u5e8a\u8bd5\u9a8c\u5747\u4e3aHLA-A*02\u9650\u5236\u6027\u7684\u975e\u7efc\u5408\u9009\u62e9<\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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\u672c\u6587\u7531Oncolab\u5fae\u4fe1\u516c\u4f17\u53f7\u7ffb\u8bd1\u6574\u7406\u81eaOncoimmunology: A Practical Guide for Cancer Immunotherapy\uff0c\u4ec5\u7528\u4e8e\u5b66\u4e60\u4ea4\u6d41\u4f7f\u7528\uff0c\u5982\u9700\u8d2d\u4e70\u539f\u7248\u4e66\u7c4d\u53ef\u70b9\u51fb\u9605\u8bfb\u539f\u6587\u8d2d\u4e70\u3002<\/span>
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\u2014 THE  END \u2014<\/span><\/p>\n


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\u6765\u6e90 | Oncoimmunology: A Practical Guide <\/span><\/p>\n

for Cancer Immunotherapy<\/span><\/p>\n

\u521d\u7a3f\u7ffb\u8bd1 | \u66fe\u4e16\u7eaa<\/span><\/p>\n

\u56fe\u6587\u6392\u7248 | \u6797\u5b50\u7545 \u9093\u8d8a\u534e<\/span><\/span><\/p>\n

\u5ba1\u6838\u4fee\u6539 | \u738b\u5764<\/span><\/p>\n

\uff08\u8f6c\u8f7d\u8bf7\u4fdd\u7559\u6b64\u90e8\u5206\u5185\u5bb9\uff09<\/span><\/strong><\/p>\n


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\u2589  \u5f80\u671f\u63a8\u9001\u5408\u8f91<\/strong><\/strong><\/section>\n
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\u80bf\u7624\u514d\u75ab\u5b66\u6700\u65b0\u6587\u732e<\/span><\/a>
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\u53ef\u4ee5\u67e5\u8be22024\u5e74\u6700\u65b0SCI\u671f\u520a\u5f71\u54cd\u56e0\u5b50\u53ca\u5206\u533a\u5566\uff01<\/span><\/a>
\u514d\u75ab\u5b66\u62fe\u9057\u7cfb\u5217<\/span><\/a><\/p>\n

\u80bf\u7624\u514d\u75ab\u5b66\u7cfb\u5217<\/span><\/a><\/p>\n

\u795e\u7ecf\u79d1\u5b66\u539f\u7406\u7cfb\u5217<\/span><\/a><\/p>\n

ACIR\u6587\u732e\u901f\u9012<\/span><\/a><\/p>\n

SCI\u8bba\u6587\u4f5c\u56fe<\/span><\/a><\/p>\n

SCI\u8bba\u6587\u5199\u4f5c\u53ca\u6295\u7a3f<\/span><\/a><\/p>\n

\u751f\u4fe1\u5165\u95e8\u5b66\u4e60\u7b14\u8bb0<\/span><\/a><\/p>\n

R\u8bed\u8a00\u57fa\u7840\u4e0e\u5355\u7ec6\u80de\u5206\u6790\u5b9e\u6218\u89c6\u9891\u8bfe\u7a0b<\/span><\/a><\/p>\n

\u751f\u7269\u5b66\u5b9e\u9a8c\u6280\u672f\u53ca\u5e38\u7528\u8f6f\u4ef6<\/span><\/a><\/p>\n

\u5e38\u7528\u5b9e\u9a8c<\/span>\u4eea\u5668\u7b80\u4ecb\u53ca\u64cd\u4f5c\u89c6\u9891<\/span><\/a><\/span><\/p>\n

\u5e38\u7528\u7535\u8111\u8f6f\u4ef6\u4f7f\u7528\u6559\u7a0b<\/span><\/a><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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\u5173\u6ce8\u672c\u53f7~<\/span>
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\u52a0\u5165\u8bfb\u8005\u4ea4\u6d41\u7fa4~<\/span><\/p>\n

\uff08\u6dfb\u52a0\u8bf7\u5907\u6ce8\u5355\u4f4d\u59d3\u540d\uff09<\/span><\/p>\n


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\u52a0\u5165\u77e5\u8bc6\u661f\u7403~<\/span><\/p>\n


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\u70b9\u4eae\u8d5e\u4e0e\u5728\u770b <\/span><\/p>\n

\u8ba9\u66f4\u591a\u4eba\u770b\u5230<\/span><\/p>\n

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\u672c\u7bc7\u6587\u7ae0\u6765\u6e90\u4e8e\u5fae\u4fe1\u516c\u4f17\u53f7:OncoLab<\/p>\n<\/blockquote>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

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