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19.1 \u6076\u6027\u9ed1\u8272\u7d20\u7624<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u73b0\u9636\u6bb5\u7814\u7a76\u53d1\u73b0\uff0c\u53ef\u4ea7\u751f\u8272\u7d20\u7684\u9ed1\u8272\u7d20\u7ec6\u80de\u7684\u6076\u6027\u8f6c\u5316\u4f1a\u4fc3\u8fdb\u9ed1\u8272\u7d20\u7624\u5728\u4e0d\u540c\u7ec4\u7ec7\u4e2d\u7684\u53d1\u5c55\uff0c\u6076\u5316\u5f62\u6210\u4e0d\u540c\u7684\u80bf\u7624\u4e9a\u578b(\u5982\u76ae\u80a4\u3001\u7c98\u819c\u3001\u8461\u8404\u819c\u9ed1\u8272\u7d20\u7624)\uff0c\u6bcf\u4e00\u4e2a\u4e9a\u578b\u90fd\u6709\u5176\u7279\u5b9a\u7684\u57fa\u56e0\u6539\u53d8<\/span>\u3002\u76ae\u80a4\u9ed1\u8272\u7d20\u7624\u5e38\u89c1\u4e8e\u897f\u65b9\uff0c\u7ea6\u6bcf10\u4e07\u4eba\u4e2d\u5c31\u670915-25\u4eba\u786e\u8bca\u8be5\u75be\u75c5\uff0c\u60a3\u8005\u786e\u8bca\u65f6\u7684\u4e2d\u4f4d\u5e74\u9f84\u4e3a57\u5c81\uff0c\u7d2b\u5916\u7ebf\u662f\u8bf1\u53d1\u8be5\u75be\u75c5\u7684\u4e3b\u8981\u81f4\u75c5\u56e0\u7d20\uff0c\u4e0e\u897f\u65b9\u4e0d\u540c\u7684\u662f\uff0c\u5728\u4e9a\u6d32\u9ecf\u819c\u9ed1\u8272\u7d20\u7624\u66f4\u5e38\u89c1\u3002\u76ae\u80a4\u9ed1\u8272\u7d20\u7624\u662f\u5e74\u8f7b\u4eba\u6700\u5e38\u89c1\u7684\u764c\u75c7\u4e4b\u4e00\uff0c\u5176\u65e9\u671f\u8f6c\u79fb\u7684\u7279\u6027\u5bfc\u81f475%\u4e0e\u76ae\u80a4\u764c\u76f8\u5173\u7684\u6b7b\u4ea1\u90fd\u4e0e\u5176\u6709\u5173\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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19.2 CD8+<\/sup>T\u7ec6\u80de\u5bf9\u9ed1\u8272\u7d20\u7624\u7684\u53cd\u5e94<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u7814\u7a76\u53d1\u73b0\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u7684\u5916\u5468\u8840\u548c\u8f6c\u79fb\u7076\u4e2d\u5b58\u5728\u9488\u5bf9\u4e0d\u540c\u80bf\u7624\u6297\u539f(\u5305\u62ec\u65b0\u6297\u539f)\u7684CD8+<\/sup>T\u7ec6\u80de\u3002\u4f46\u662f\u5373\u4f7f\u5728\u8fd9\u79cd\u591a\u79cd\u80bf\u7624\u53cd\u5e94\u6027T\u7ec6\u80de\u5b58\u5728\u7684\u60c5\u51b5\u4e0b\uff0c\u75be\u75c5\u4e5f\u4f1a\u7ee7\u7eed\u53d1\u751f\u8fdb\u5c55\u3002\u73b0\u5728\u5df2\u7ecf\u786e\u5b9a\u7684\u662f\uff0c\u9ed1\u8272\u7d20\u7624\u7684\u8fdb\u5c55\u662f\u7531\u4e8e\u591a\u79cd\u673a\u5236\u5bfc\u81f4T\u7ec6\u80de\u529f\u80fd\u51cf\u5f31\u9020\u6210\u7684\u3002\u5176\u4e2d\uff0c\u80bf\u7624\u7ec6\u80de\u7684\u76f4\u63a5\u63a5\u89e6\u5bf9T\u7ec6\u80de\u6d3b\u6027\u7684\u6291\u5236\u4f3c\u4e4e\u53d1\u6325\u4e86\u91cd\u8981\u4f5c\u7528\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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19.3 T\u7ec6\u80de\u6fc0\u6d3b\u7684\u68c0\u67e5\u70b9\u63a7\u5236<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5728\u8868\u9762TCR\u4e0e\u643a\u5e26\u9ed1\u8272\u7d20\u7624\u6297\u539f\u80bd\u7684MHC-I\u590d\u5408\u7269\u7ed3\u5408\u540e\uff0c\u9ed1\u8272\u7d20\u7624\u7279\u5f02\u6027CD8+<\/sup>T\u7ec6\u80de<\/span>\u88ab\u6fc0\u6d3b\uff0c\u968f\u540e\u91ca\u653e<\/span>\u5e72\u6270\u7d20\u03b3\uff0c\u8bf1\u5bfc\u5468\u56f4\u9ed1\u8272\u7d20\u7624\u7ec6\u80de\u8868\u8fbePD-L1(\u4e5f\u79f0\u4e3aB7-H1\u548cCD274)\uff0c\u5982Fig. 19.1<\/span>\u6240\u793a\u3002PD-L1\u4e0eCD8+<\/sup>T\u7ec6\u80de\u4e0a\u7684\u6291\u5236\u6027\u5171\u53d7\u4f53PD-1\u7ed3\u5408\uff0c\u4ece\u800c\u524a\u5f31T\u7ec6\u80de\u7684\u6548\u5e94\u5668\u529f\u80fd(\u7ec6\u80de\u6eb6\u89e3\u9897\u7c92\u548c\u7ec6\u80de\u56e0\u5b50\u91ca\u653e)\uff0c\u6291\u5236\u5176\u589e\u6b96\u3002\u6b64\u5916\uff0cPD-1\u8fd8\u80fd\u4e0ePD-L2<\/span>\u7ed3\u5408\uff0c\u4f46\u662f\u5728\u9ed1\u8272\u7d20\u7624\u7ec6\u80de\u4e0a\u68c0\u6d4b\u4e0d\u5230\u8fd9\u79cd\u7ed3\u5408\u3002\u6b63\u5e38\u60c5\u51b5\u4e0b\uff0cT\u7ec6\u80de\u4e2d\u7684PD-1\u4fe1\u53f7\u5bf9\u673a\u4f53\u7ef4\u6301\u81ea\u8eab\u514d\u75ab\u8010\u53d7\u5177\u6709\u91cd\u8981\u610f\u4e49\uff0cPD-1\u57fa\u56e0\u6572\u9664\u5c0f\u9f20\u51fa\u73b0\u81ea\u53d1\u7684\u81ea\u8eab\u514d\u75ab\u53cd\u5e94\u8bc1\u660e\u4e86\u8fd9\u4e00\u70b9\u3002\u56e0\u6b64\uff0cPD-1\u662f\u6291\u5236CD8+<\/sup>T\u7ec6\u80de\u529f\u80fd\u7684\u91cd\u8981\u68c0\u67e5\u70b9\uff0c\u9ed1\u8272\u7d20\u7624\u7ec6\u80de\u901a\u8fc7\u8868\u8fbePD-L1\uff0c\u83b7\u5f97\u4e86\u76f4\u63a5\u964d\u4f4eT\u7ec6\u80de\u6d3b\u6027\u7684\u80fd\u529b<\/span>(Fig. 19.2<\/span>)\u3002\u800c\u5728\u4ece\u80bf\u7624\u7ec4\u7ec7\u548c\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u5916\u5468\u8840\u4e2d\u5206\u79bb\u51fa\u7684\u65b0\u6297\u539f\u7279\u5f02\u6027CD8+<\/sup>T\u7ec6\u80de\u4e0a\uff0c\u4e5f\u53d1\u73b0\u4e86PD-1\u7684\u8868\u8fbe\uff0c\u8fd9\u4e3a\u5f00\u53d1\u963b\u65adPD-1\u548cPD-L1\u4e4b\u95f4\u76f8\u4e92\u4f5c\u7528\u7684\u6cbb\u7597\u7b56\u7565\u63d0\u4f9b\u4e86\u7406\u8bba\u57fa\u7840(Fig. 19.2<\/span>)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Fig. 19.1<\/span> CD8+<\/sup>T\u7ec6\u80de\u65c1\u8fb9\u7684\u9ed1\u8272\u7d20\u7624\u7ec6\u80de\u8868\u8fbePD-L1\u3002\u901a\u8fc7\u514d\u75ab\u7ec4\u5316\u67d3\u8272\u6807\u8bb0\u9ed1\u8272\u7d20\u7624\u6dcb\u5df4\u7ed3\u75c5\u53d8\u4e2d\u7684CD8+<\/sup>T\u7ec6\u80de(\u68d5\u8272)\u548c\u9ed1\u8272\u7d20\u7624\u7ec6\u80de(PD-L1, \u7ea2\u8272)\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Fig. 19.2<\/span> \u9ed1\u8272\u7d20\u7624\u7ec6\u80de\u4f9d\u8d56PD-1\u6291\u5236T\u7ec6\u80de\u6d3b\u6027<\/span><\/p>\n

(A)\u80bf\u7624\u6d78\u6da6\u6027T\u7ec6\u80de\u901a\u8fc7\u5176T\u7ec6\u80de\u53d7\u4f53(TCR)\u8bc6\u522b\u9ed1\u8272\u7d20\u7624\u7ec6\u80de\uff0c\u968f\u540eTCR\u4e0e\u7279\u5b9a\u7684HLA I\u7c7b\u6297\u539f\u8868\u9762\u590d\u5408\u4f53\u7ed3\u5408\uff0c\u6d3b\u5316T\u7ec6\u80de\u3002\u968f\u540e\u88ab\u6fc0\u6d3b\u7684T\u7ec6\u80de\u91ca\u653e\u7ec6\u80de\u6eb6\u89e3\u9897\u7c92\u5e76\u5206\u6ccc\u5e72\u6270\u7d20\u03b3; <\/span>(B)\u5e72\u6270\u7d20\u03b3\u8bf1\u5bfc\u9ed1\u8272\u7d20\u7624\u7ec6\u80de\u8868\u8fbePD-L1\uff0c\u5e76\u4e0e\u6291\u5236\u6027\u53d7\u4f53PD-1\u7ed3\u5408\uff0c\u4ece\u800c\u6291\u5236T\u7ec6\u80de\u7684\u6fc0\u6d3b; (C)\u6297\u4f53\u963b\u65adPD-1\u4e0e\u5176\u914d\u4f53PD-L1\u4e4b\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\uff0c\u4f7fT\u7ec6\u80de\u4ece\u6291\u5236\u4fe1\u53f7\u4e2d\u91ca\u653e\u51fa\u6765\uff0c\u6062\u590d\u5176\u6d3b\u6027\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5f71\u54cdT\u7ec6\u80de\u6d3b\u5316\u7684\u53e6\u4e00\u4e2a\u5173\u952e\u68c0\u67e5\u70b9\u662fCTLA-4\uff0c\u4e0ePD-L1\u76f8\u53cd\uff0c\u5b83\u5728\u9ed1\u8272\u7d20\u7624\u7ec6\u80de\u4e0a\u4e0d\u8868\u8fbe\u3002\u5176\u914d\u4f53\u662fCD80\u548cCD86\uff0c\u5747\u5728\u6297\u539f\u5448\u9012\u7ec6\u80de\u4e0a\u8868\u8fbe\uff0c\u5982\u6811\u7a81\u72b6\u7ec6\u80de(DC)\u3002\u6811\u7a81\u72b6\u7ec6\u80de\u80fd\u591f\u5728\u5916\u5468\u4e0e\u80bf\u7624\u6297\u539f\u7ed3\u5408\uff0c\u5e76\u8fc1\u79fb\u5230\u5f15\u6d41\u6dcb\u5df4\u7ed3\uff0c\u5728\u90a3\u91cc\u6fc0\u6d3bT\u7ec6\u80de\u3002TCR\u7279\u5f02\u6027\u8bc6\u522b\u80bf\u7624MHC\u590d\u5408\u7269\u540e\uff0cT\u7ec6\u80de\u8868\u9762\u5f00\u59cb\u8868\u8fbeCTLA-4\uff0cCTLA-4\u4e0epAPC\uff08\u4e13\u804c\u6297\u539f\u5448\u9012\u7ec6\u80de\uff09\u4e0a\u7684CD80\/CD86\u7ed3\u5408\uff0c\u4ece\u800c\u6291\u5236T\u7ec6\u80de\u7684\u6fc0\u6d3b\u3002CTLA-4\u548cPD-1\u4e00\u6837\uff0c\u662f\u673a\u4f53\u7ef4\u6301\u81ea\u8eab\u514d\u75ab\u8010\u53d7\u7684\u5173\u952e\u56e0\u7d20\u4e4b\u4e00\uff0c\u7f3a\u4e4fCTLA-4\u7684\u5c0f\u9f20\u8868\u73b0\u51fa\u5927\u91cf\u7684\u6dcb\u5df4\u589e\u6b96\u548c\u65e9\u671f\u6b7b\u4ea1\u73b0\u8c61\u3002\u867d\u7136CTLA-4\u4ec5\u5728\u5305\u62ec\u8c03\u8282\u6027T\u7ec6\u80de(Treg)\u5728\u5185\u7684\u5404\u79cdT\u7ec6\u80de\u4e0a\u8868\u8fbe\uff0c\u4f46PD-1\u9664\u4e86\u5728T\u7ec6\u80de\u4e0a\u8868\u8fbe\u5916\uff0c\u4e5f\u5728\u81ea\u7136\u6740\u4f24(NK)\u7ec6\u80de\u548cB\u7ec6\u80de\u4e0a\u6709\u8868\u8fbe\uff0c\u6240\u4ee5\u9664\u4e86T\u7ec6\u80de\uff0c\u8fd9\u4e9b\u7ec6\u80de\u7684\u6d3b\u6027\u4e5f\u5f88\u53ef\u80fd\u53d7\u5230\u9488\u5bf9\u514d\u75ab\u68c0\u67e5\u70b9\u7684\u6297\u4f53\u7684\u5f71\u54cd\u3002\u867d\u7136\u5728\u8fd9\u7bc7\u7efc\u8ff0\u4e2d\uff0c\u6211\u4eec\u5e76\u672a\u8be6\u7ec6\u8ba8\u8bba\u590d\u6742\u7684\u751f\u7269\u5b66\u7406\u8bba\uff0c\u4f46\u5e94\u8be5\u8bb0\u4f4f\u7684\u662f\u2014PD-1\u548cCTLA-4\u53ef\u4ee5\u88ab\u8ba4\u4e3a\u662f\u9650\u5236\u80bf\u7624\u53cd\u5e94\u6027CD8+<\/sup>T\u7ec6\u80de\u6548\u5e94\u529f\u80fd\u7684\u514d\u75ab\u5239\u8f66(\u68c0\u67e5\u70b9)\u3002\u9488\u5bf9\u8fd9\u4e9b\u5239\u8f66(\u68c0\u67e5\u70b9)\u4f7f\u7528\u6cbb\u7597\u6027\u6297\u4f53\uff0c\u963b\u65ad\u53d7\u4f53-\u914d\u4f53\u7684\u76f8\u4e92\u4f5c\u7528\uff0c\u53ef\u4ee5\u5728\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\u8bf1\u5bfc\u663e\u8457\u548c\u6301\u4e45\u7684\u4e34\u5e8a\u53cd\u5e94\uff0c\u6b63\u5982\u4e0b\u6587\u6240\u8ff0\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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19.4 \u68c0\u67e5\u70b9\u963b\u65ad\u7597\u6cd5<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u57282011\u5e74\u4e4b\u524d\uff0c\u60a3\u6709\u665a\u671f\u8f6c\u79fb\u75be\u75c5\u7684\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e00\u822c\u63a5\u53d7\u7684\u662f\u5316\u7597\u836f\u7269(\u8fbe\u5361\u5df4\u55ea\u3001\u66ff\u83ab\u5511\u80fa\u3001\u798f\u83ab\u53f8\u6c40)\u7684\u6807\u51c6\u5316\u59d1\u606f\u6cbb\u7597\u3002\u800c\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u65ad\u7597\u6cd5\u4ecd\u7f3a\u4e4f\u8bc1\u660e\u76f8\u5173\u836f\u7269\u5bf9\u60a3\u8005\u603b\u4f53\u751f\u5b58\u7387\u6709\u5f71\u54cd\u7684\u5927\u578b\u968f\u673a\u8bd5\u9a8c\u30022011\u5e74\uff0c\u57fa\u4e8e\u4e24\u9879\u968f\u673a\u8bd5\u9a8c\uff0c\u9996\u4e2a\u9488\u5bf9CTLA-4\u7684\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u65ad\u6297\u4f53(\u4f0a\u5339\u5355\u6297\uff0c\u5168\u4ebaIgG1\u6297\u4f53)\u83b7\u5f97\u7f8e\u56fd\u98df\u54c1\u548c\u836f\u7269\u7ba1\u7406\u5c40(FDA)\u548c\u6b27\u6d32\u836f\u54c1\u7ba1\u7406\u5c40(EMA)\u7684\u6279\u51c6\uff0c\u7528\u4e8e\u6cbb\u7597\u665a\u671f\u75be\u75c5\u60a3\u8005\u3002\u4e00\u9879\u8bd5\u9a8c\u6bd4\u8f83\u4e86\u4f0a\u5339\u5355\u6297\u548c\u57fa\u4e8e\u591a\u80bd\u7684\u75ab\u82d7\u5728\u65e2\u5f80\u65e0\u6cd5\u5207\u9664\u7684\u665a\u671f\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\u7684\u4f5c\u7528\u3002\u800c\u5728\u53e6\u4e00\u9879\u8bd5\u9a8c\u4e2d\uff0c\u60a3\u8005\u63a5\u53d7\u8fbe\u5361\u5df4\u55ea\u8054\u5408\u4f0a\u5339\u5355\u6297\u6216\u8fbe\u5361\u5df4\u55ea\u8054\u5408\u5b89\u6170\u5242\u6cbb\u7597\u3002\u8fd9\u4e24\u9879\u7814\u7a76\u90fd\u8868\u660e\uff0c\u63a5\u53d7\u4f0a\u5339\u5355\u6297\u6cbb\u7597\u7684\u60a3\u8005\u75c5\u60c5\u6709\u663e\u8457\u6539\u5584\uff0c\u6cbb\u7597\u7684\u6709\u6548\u7387\u572810%\u81f315%\u4e4b\u95f4\u3002\u7531\u4e8eCTLA-4\u5728\u7ef4\u6301\u81ea\u8eab\u514d\u75ab\u8010\u53d7\u65b9\u9762\u7684\u4f5c\u7528\uff0c\u5b83\u7684\u5168\u8eab\u6027\u963b\u65ad\u4e5f\u5177\u6709\u4e00\u5b9a\u6bd2\u526f\u4f5c\u7528\u3002\u5728\u67d0\u4e9b\u60c5\u51b5\u4e0b\uff0c\u63a5\u53d7\u4f0a\u5339\u5355\u6297\u5355\u4e00\u6cbb\u7597\u7684\u60a3\u8005\u4e2d\uff0c10%-15%\u7684\u60a3\u8005\u4f1a\u51fa\u73b0\u5b9a\u4e49\u4e3a3-4\u7ea7\u7684\u5371\u53ca\u751f\u547d\u7684\u4e0d\u826f\u4e8b\u4ef6(AE)\u3002\u6700\u5e38\u89c1\u76843-4\u7ea7AE\u662f\u7ed3\u80a0\u708e\u3001\u76ae\u75b9\u548c\u5185\u5206\u6ccc\u75be\u75c5\u3002\u4f7f\u7528\u4f0a\u5339\u5355\u6297\u8fdb\u884c\u5168\u9762\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u65ad\u662f\u7b2c\u4e00\u79cd\u8fd0\u7528\u4e8e\u9ed1\u8272\u7d20\u7624\u6cbb\u7597\u7684\u514d\u75ab\u7597\u6cd5\uff0c\u6709\u6587\u732e\u8bc1\u660e\uff0c\u5728\u4e00\u7ec4\u4f7f\u7528\u8be5\u7597\u6cd5\u7684\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\uff0c\u60a3\u8005\u7684\u603b\u4f53\u7597\u6548\u8f83\u5176\u4ed6\u7597\u6cd5\u6709\u6240\u6539\u5584\u3002\u8be5\u7597\u6cd5\u662f\u5229\u7528\u514d\u75ab\u7597\u6cd5\u6cbb\u7597\u9ed1\u8272\u7d20\u7624\u7684\u4e00\u4e2a\u91cc\u7a0b\u7891\uff08\u5173\u4e8e\u57fa\u4e8eCTLA-4\u7684\u6cbb\u7597\u7684\u8be6\u7ec6\u4fe1\u606f\u5728\u672c\u4e66\u7684\u53e6\u4e00\u7ae0\u4e2d\u7ed9\u51fa\uff09\u3002\u63a5\u4e0b\u6765\u5c06\u8981\u4ecb\u7ecd\u7684\u662f\u57fa\u4e8e\u9488\u5bf9PD-1\u514d\u75ab\u68c0\u67e5\u70b9\u7684\u6297\u4f53\u7684\u6210\u529f\u6cbb\u7597\u6848\u4f8b<\/span>\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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19.5 \u7ecf\u6279\u51c6\u7684\u6297PD-1\u6297\u4f53<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5728\u4f0a\u5339\u5355\u6297\u4e4b\u540e\uff0c\u4e24\u79cd\u9488\u5bf9\u68c0\u67e5\u70b9PD-1\u7684\u6297\u4f53\u88ab\u6279\u51c6\u7528\u4e8e\u6cbb\u7597\u4e0d\u53ef\u5207\u9664\u548c\u8f6c\u79fb\u6027\u9ed1\u8272\u7d20\u7624\u3002FDA\u548cEMA\u5206\u522b\u6279\u51c6\u4e86\u7eb3\u6b66\u5355\u6297\u548c\u6d3e\u59c6\u5355\u6297\uff0c\u5b83\u4eec\u662f\u4e00\u79cd\u5b8c\u5168\u4eba\u6e90\u5316\u7684IgG4\u6297\u4f53\u3002\u57fa\u4e8e\u7eb3\u6b66\u5355\u6297\u548c\u6d3e\u59c6\u5355\u6297\u7684\u6cbb\u7597\u5c55\u793a\u51fa\u4e86\u66f4\u9ad8\u7684\u6301\u4e45\u5e94\u7b54\u7387\uff0c\u800c\u4e0e\u4f0a\u5339\u5355\u6297\u6cbb\u7597\u76f8\u6bd4\uff0cAE\u53d1\u751f\u7684\u6982\u7387\u8981\u4f4e\u5f97\u591a\u3002\u4e0b\u9762\uff0c\u6211\u4eec\u5217\u51fa\u4e86\u4e0e\u6297\u4f53\u6279\u51c6\u76f8\u5173\u7684\u4e00\u4e9b\u4e34\u5e8a\u8bd5\u9a8c\u7ed3\u679c(Table. 19.1<\/span>)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Table <\/span><\/span>19.1<\/span> <\/span>\u4e0e\u6279\u51c6PD-1\u68c0\u67e5\u70b9\u963b\u65ad\u7597\u6cd5\u6709\u5173\u7684\u4e09\u671f\u4e34\u5e8a\u8bd5\u9a8c\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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19.6 Nivolumab\uff08\u7eb3\u6b66\u5355\u6297\uff09<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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2014\u5e7412\u6708\uff0cFDA \u6279\u51c6\u7eb3\u6b66\u5355\u6297\u7528\u4e8e\u665a\u671f\u9ed1\u8272\u7d20\u7624\u7684\u6cbb\u7597\u30022015\u5e746\u6708\uff0cEMA \u57fa\u4e8e\u4ee5\u4e0b\u4e24\u9879\u7814\u7a76\u6279\u51c6\u7eb3\u6b66\u5355\u6297\u53ef\u7528\u4e8e\u665a\u671f\u9ed1\u8272\u7d20\u7624\u7684\u6cbb\u7597: CheckMate 066(\u968f\u673a\u53cc\u76f23\u671f\u8bd5\u9a8c\uff0c\u5305\u62ec418\u540d\u9ed1\u8272\u7d20\u7624\u60a3\u8005)\u548c CheckMate 037(\u5f00\u653e\u6807\u7b7e3\u671f\u8bd5\u9a8c\uff0c\u5305\u62ec405\u540d\u9ed1\u8272\u7d20\u7624\u60a3\u8005)(Table.19.1<\/span>)\u3002\u5728\u8fd9\u4e24\u9879\u7814\u7a76\u4e2d\uff0c\u53c2\u8bd5\u4eba\u5458\u7eb3\u6b66\u5355\u6297\u7684\u6bcf\u4e24\u5468\u670d\u7528\u91cf\u4e3a3mg\/kg(\u4f53\u91cd)\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5728CheckMate 066\u8bd5\u9a8c\u4e2d\uff0c\u672a\u7ecf\u6cbb\u7597\u7684\u60a3\u8005\u63a5\u53d7\u4e86\u7eb3\u6b66\u5355\u6297\u6216\u8fbe\u5361\u5df4\u55ea\u6cbb\u7597\u3002\u63a5\u53d7\u7eb3\u6b66\u5355\u6297\u6cbb\u7597\u7684\u60a3\u8005\u76841\u5e74\u603b\u5b58\u6d3b\u7387(OSR)\u4e3a72.9%\uff0c\u800c\u63a5\u53d7\u8fbe\u5361\u5df4\u55ea\u6cbb\u7597\u7684\u60a3\u8005\u76841\u5e74\u603b\u5b58\u6d3b\u7387\u4e3a42.1%\u3002\u7eb3\u6b66\u5355\u6297\u7684\u4e2d\u4f4d\u65e0\u8fdb\u5c55\u751f\u5b58\u671f(PFS)\u4e3a5.1\u4e2a\u6708\uff0c\u8fbe\u5361\u5df4\u55ea\u7684\u4e3a2.2\u4e2a\u6708\u3002\u7eb3\u6b66\u5355\u6297\u7684\u603b\u4f53\u5e94\u7b54\u7387(ORR)\u4e3a40.0%\uff0c\u8fbe\u5361\u5df4\u55ea\u4e3a13.9%\u3002\u6b64\u5916\u7eb3\u6b66\u5355\u6297\u6cbb\u7597\u7684\u60a3\u8005\u7684\u5b8c\u5168\u7f13\u89e3\u7387\u4e3a7.6%\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5728CheckMate 037\u8bd5\u9a8c\u4e2d\uff0c\u60a3\u8005\u63a5\u53d7\u4e86\u7eb3\u6b66\u5355\u6297\u6216\u5316\u7597\uff08\u8fbe\u5361\u5df4\u55ea\u6216\u5361\u94c2\u8054\u5408\u7d2b\u6749\u9187[\u7814\u7a76\u4eba\u5458\u9009\u62e9]\uff09\u6cbb\u7597\u3002\u53c2\u4e0e\u672c\u7814\u7a76\u7684\u60a3\u8005\u63a5\u53d7\u4e86\u7eb3\u6b66\u5355\u6297\u6216BRAF\u6291\u5236\u5242\u7684\u9884\u5904\u7406\uff08\u9488\u5bf9BRAF(V600E)\u7a81\u53d8\u9ed1\u8272\u7d20\u7624\uff09\u3002\u7eb3\u6b66\u5355\u6297\u548c\u5316\u7597\u7ec4\u7684ORR\u5206\u522b\u4e3a31.7%\u548c10.6%\u3002\u503c\u5f97\u6ce8\u610f\u7684\u662f\uff0c\u8fd9\u9879\u8bd5\u9a8c\u540c\u65f6\u4e5f\u8868\u660e\uff0c\u63a5\u53d7\u4f0a\u5339\u5355\u6297\u9884\u6cbb\u7597\u7684\u60a3\u8005\u4ecd\u7136\u53ef\u4ee5\u662f\u7eb3\u6b66\u5355\u6297\u5e94\u7b54\u8005\u3002\u8fd9\u4e00\u7ed3\u679c\u63a8\u52a8\u4e86FDA\u57282014\u5e7412\u6708\u5bf9\u7eb3\u6b66\u5355\u6297\u8fd0\u7528\u4e8e\u4e34\u5e8a\u7684\u6279\u51c6\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u603b\u800c\u8a00\u4e4b\uff0c\u60a3\u8005\u5bf9\u4e8e\u7eb3\u6b66\u5355\u6297\u7684\u5e94\u7b54\u7387\u8868\u73b0\u572830%\u523040%\u4e4b\u95f4\uff0c\u663e\u8457\u9ad8\u4e8e\u5df2\u62a5\u9053\u7684\u4f0a\u5339\u5355\u6297\u6cbb\u7597\u7684\u5e94\u7b54\u7387\uff0c\u800c\u4e14\u7eb3\u6b66\u5355\u6297\u7684\u8010\u53d7\u6027\u76f8\u8f83\u4f0a\u5339\u5355\u6297\u4e5f\u8981\u597d\u5f97\u591a\u3002\u5f53\u7136\uff0c\u5176\u4e5f\u5177\u6709\u526f\u4f5c\u7528\uff0c\u56e0\u4e3aPD-1\u548cCTLA-4\u4e00\u6837\uff0c\u4e5f\u53c2\u4e0e\u7ef4\u6301\u81ea\u8eab\u514d\u75ab\u8010\u53d7\uff0c\u4f46\u5176\u6bd2\u526f\u4f5c\u7528\u53d1\u751f\u6982\u7387\u4f4e\u3002\u5728CheckMate 066\u548cCheckMate 037\u7814\u7a76\u4e2d\uff0c\u7eb3\u6b66\u5355\u6297\u6cbb\u7597\u7ec4\u6700\u5e38\u89c1\u7684\u526f\u4f5c\u7528\u662f\u75b2\u52b3\u3001\u7619\u75d2\u548c\u6076\u5fc3\u3002\u51fa\u73b03\u7ea7\u62164\u7ea7\u836f\u7269\u76f8\u5173\u4e0d\u826f\u4e8b\u4ef6\u517111\u4f8b\uff0c\u5206\u522b\u53607%\uff08CheckMate066\uff09\u548c 5%\uff08CheckMate037\uff09\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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<\/span>\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><\/span><\/span>
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\u2014<\/span> <\/span>T<\/span>H<\/span>E<\/span> <\/span> <\/span>E<\/span>N<\/span>D<\/span> <\/span>\u2014<\/span><\/span><\/p>\n


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\u6765<\/span>\u6e90<\/span> <\/span>|<\/span> <\/span>O<\/span>n<\/span>c<\/span>o<\/span>i<\/span>m<\/span>m<\/span>u<\/span>n<\/span>o<\/span>l<\/span>o<\/span>g<\/span>y<\/span>:<\/span> <\/span>A<\/span> <\/span>P<\/span>r<\/span>a<\/span>c<\/span>t<\/span>i<\/span>c<\/span>a<\/span>l<\/span> <\/span>G<\/span>u<\/span>i<\/span>d<\/span>e<\/span> <\/span><\/span><\/section>\n
f<\/span>o<\/span>r<\/span> <\/span>C<\/span>a<\/span>n<\/span>c<\/span>e<\/span>r<\/span> <\/span>I<\/span>m<\/span>m<\/span>u<\/span>n<\/span>o<\/span>t<\/span>h<\/span>e<\/span>r<\/span>a<\/span>p<\/span>y<\/span><\/span><\/section>\n
\u4f5c<\/span>\u8005<\/span> <\/span>|<\/span> <\/span><\/span><\/span>Annette Paschen and Dirk Schadendorf<\/span><\/span><\/section>\n
\u7ffb<\/span>\u8bd1<\/span> <\/span>|<\/span> <\/span>\u9648\u8389\u8679 \u6e29\u946b \u90d1\u68a6\u6021<\/span><\/span><\/span><\/span><\/section>\n
\u7f16<\/span>\u8f91<\/span>\u6392<\/span>\u7248<\/span> <\/span>| \u90ed\u5b50<\/span><\/span><\/span><\/span><\/span><\/span><\/section>\n
\u521d<\/span>\u5ba1<\/span> <\/span>|<\/span> \u5218\u7389\u5a07<\/span> \u4f55\u4e3d\u5a1c<\/span><\/span><\/span><\/section>\n
\u7ec8<\/span>\u5ba1<\/span> <\/span>|<\/span> \u738b<\/span>\u5764<\/span><\/span><\/span><\/span><\/section>\n
\uff08<\/span>\u8f6c<\/span>\u8f7d<\/span>\u8bf7<\/span>\u4fdd<\/span>\u7559<\/span>\u6b64<\/span>\u90e8<\/span>\u5206<\/span>\u5185<\/span>\u5bb9<\/span>\uff09<\/span><\/span><\/strong><\/section>\n


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\u2589  \u5f3a\u70c8\u63a8\u8350<\/strong><\/strong><\/p>\n

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\u2589  OncoLab\u5b9e\u9a8c\u5ba4\u7f51\u7ad9<\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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\u672c\u516c\u4f17\u53f7\u4e0a\u7684\u5f80\u671f\u6587\u7ae0\u540c\u6b65\u53d1\u5e03\u81f3\u5bf9\u5e94\u7f51\u7ad9OncoLab\u5b9e\u9a8c\u5ba4\u3002<\/p>\n

\u7f51\u7ad9\u81ea\u5e26\u68c0\u7d22\u529f\u80fd\uff0c\u53ef\u4ee5\u6839\u636e\u5173\u952e\u8bcd\u8fdb\u884c\u68c0\u7d22<\/span>\uff0c\u5e76\u4e14\u53ef\u4ee5\u6839\u636e\u65e5\u671f\u53ca\u5185\u5bb9\u5206\u7c7b<\/span>\u8fdb\u884c\u67e5\u770b ,\u5927\u5bb6\u53ef\u4ee5\u6536\u85cf\u65b9\u4fbf\u5728\u7535\u8111\u4e0a\u67e5\u770b\u3002<\/p>\n

\u7f51\u5740\u662f\uff1aoncolab.cn<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\u2589  OncoLab\u5b66\u672f\u5bfc\u822a<\/strong><\/strong><\/p>\n

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\u6b64\u5916\uff0c\u68b3\u7406\u4e86\u4e00\u4e0b\u8fd9\u51e0\u5e74\u6512\u7684\u6536\u85cf\u5939\uff0c\u505a\u4e86\u4e00\u4e2a\u5bfc\u822a\u7f51\u9875\uff0c\u5305\u542b\u5e38\u7528\u7f51\u7ad9<\/span>\u3001\u6587\u732e\u9605\u8bfb<\/span>\u3001\u8bd5\u5242\u8ba2\u8d2d<\/span>\u3001\u57fa\u91d1\u76f8\u5173<\/span>\u3001\u5b9e\u7528\u5de5\u5177<\/span>\u3001\u5e38\u7528\u6570\u636e\u5e93<\/span>\u7b49\u5206\u7c7b\u5185\u5bb9\uff0c\u5e76\u4e14\u6574\u5408\u4e86<\/span>\u767e\u5ea6\u3001\u8c37\u6b4c\u3001\u5fc5\u5e94<\/span>\u4e09\u5927\u641c\u7d22\u5f15\u64ce\u5230\u68c0\u7d22\u5de5\u5177\u4e2d\uff0c\u6b22\u8fce\u6536\u85cf\u6216\u8bbe\u7f6e\u4e3a\u4e3b\u9875\u4f7f\u7528~<\/span><\/p>\n

\u7f51\u5740\u662f\uff1adh.<\/strong><\/span>oncolab.cn<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\u2589  OncoLab\u77e5\u8bc6\u661f\u7403<\/strong><\/strong><\/strong><\/strong><\/p>\n<\/section>\n

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OncoLab\u77e5\u8bc6\u661f\u7403\u4e5f\u5df2\u5f00\u901a\uff0c\u5728\u5b66\u4e60\u672c\u516c\u4f17\u53f7\u5185\u5bb9\u7684\u8fc7\u7a0b\u4e2d\u5982\u679c\u6709\u4ec0\u4e48\u9700\u8981\u8ba8\u8bba\u4ea4\u6d41\u7684\u5730\u65b9\u53ef\u4ee5\u5728\u661f\u7403\u53d1\u8868\u7559\u8a00\uff0c\u4e5f\u53ef\u4ee5\u5206\u4eab\u4e00\u4e0b\u81ea\u5df1\u7684\u5b66\u4e60\u5fc3\u5f97\u4f53\u4f1a\uff0c\u5176\u4ed6\u5c0f\u4f19\u4f34\u770b\u5230\u4e86\u53ef\u4ee5\u79ef\u6781\u7559\u8a00\u56de\u590d\uff0c\u6211\u4e5f\u4f1a\u79ef\u6781\u53c2\u4e0e\u5176\u4e2d\uff0c\u5e76\u65f6\u5e38\u653e\u4e00\u4e9b\u5b66\u4e60\u8d44\u6599\u5728\u4e0a\u9762\uff0c\u5e0c\u671b\u5927\u5bb6\u80fd\u591f\u5728\u79ef\u6781\u4ea4\u6d41\u4e92\u5e2e\u4e92\u52a9\u4e2d\u5171\u540c\u8fdb\u6b65~<\/p>\n

\u8be5\u661f\u7403\u7528\u4e8eOncoLab\u516c\u4f17\u53f7\u8bfb\u8005\u4ea4\u6d41\u5b66\u4e60\u4f7f\u7528\uff0c\u6c38\u4e45\u514d\u8d39<\/span>\u3002<\/span><\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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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><\/span><\/p>\n


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


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

\u70b9\u4eae\u8d5e\u4e0e\u5728\u770b <\/span><\/section>\n
\u8ba9\u66f4\u591a\u4eba\u770b\u5230<\/span><\/span><\/section>\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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