{"id":5675,"date":"2024-06-30T12:59:04","date_gmt":"2024-06-30T04:59:04","guid":{"rendered":"http:\/\/dh.oncolab.cn\/index.php\/2024\/06\/30\/%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac32%e7%ab%a0%ef%bc%9a1%e6%9c%9f%e8%af%95%e9%aa%8c%e4%b8%ad%e7%9a%84%e5%85%8d%e7%96%ab%e7%96%97%e6%b3%95%ef%bc%88%e4%b8%8a%ef%bc%89\/"},"modified":"2024-06-30T12:59:04","modified_gmt":"2024-06-30T04:59:04","slug":"%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac32%e7%ab%a0%ef%bc%9a1%e6%9c%9f%e8%af%95%e9%aa%8c%e4%b8%ad%e7%9a%84%e5%85%8d%e7%96%ab%e7%96%97%e6%b3%95%ef%bc%88%e4%b8%8a%ef%bc%89","status":"publish","type":"post","link":"http:\/\/dh.oncolab.cn\/index.php\/2024\/06\/30\/%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac32%e7%ab%a0%ef%bc%9a1%e6%9c%9f%e8%af%95%e9%aa%8c%e4%b8%ad%e7%9a%84%e5%85%8d%e7%96%ab%e7%96%97%e6%b3%95%ef%bc%88%e4%b8%8a%ef%bc%89\/","title":{"rendered":"\u80bf\u7624\u514d\u75ab\u5b66-\u7b2c32\u7ae0\uff1a1\u671f\u8bd5\u9a8c\u4e2d\u7684\u514d\u75ab\u7597\u6cd5\uff08\u4e0a\uff09"},"content":{"rendered":"
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\u4e0a\u671f\u5185\u5bb9\uff1a\u80bf\u7624\u514d\u75ab\u5b66-\u7b2c31\u7ae0\uff1a\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u65ad\u53cd\u5e94\u7684\u9884\u6d4b\u56e0\u7d20(\u4e0b\uff09<\/span><\/a><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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32.1 \u5f15\u8a00<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5728\u8fc7\u53bb\u51e0\u5e74\u4e2d\uff0c\u80bf\u7624\u5b66\u9886\u57df\u7684\u836f\u7269\u5f00\u53d1\u4e13\u5bb6\u4eec\u7ecf\u5386\u4e86\u4e00\u573a\u9488\u5bf9\u4e00\u671f\u4e34\u5e8a\u8bd5\u9a8c\u8bc4\u4f30\u836f\u7269\u5206\u5b50\u7684\u9769\u547d\u3002\u56de\u987e2010\u5e74\u4ee5\u524d\uff0c\u9488\u5bf9\u514d\u75ab\u7cfb\u7edf\u7684\u6cbb\u7597\u65b9\u6cd5\u53ea\u5360\u836f\u7269\u7814\u53d1\u7684\u4e00\u5c0f\u90e8\u5206\u3002\u7136\u800c\uff0c\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\u5728\u591a\u79cd\u56fa\u4f53\u80bf\u7624\u6cbb\u7597\u4e2d\u7684\u6210\u529f\u5e26\u52a8\u4e86\u514d\u75ab\u7597\u6cd5\u7684\u8fc5\u731b\u53d1\u5c55\uff0c\u65e0\u8bba\u662f\u4f5c\u4e3a\u5355\u836f\u6cbb\u7597\u8fd8\u662f\u8054\u5408\u7597\u6cd5\u3002\u8fd9\u79cd\u53d1\u5c55\u6311\u6218\u4e86\u4f20\u7edf\u7684\u4e00\u671f\u8bd5\u9a8c\u8bbe\u8ba1\uff0c\u50ac\u751f\u4e86\u521b\u65b0\u6027\u53ca\u524d\u6240\u672a\u6709\u7684\u836f\u7269\u5f00\u53d1\u7b56\u7565\u3002\u5728\u52a0\u901f\u836f\u7269\u5f00\u53d1\u7684\u8fc7\u7a0b\u4e2d\uff0c\u9700\u6c42\u7a7a\u524d\u7d27\u8feb\uff0c\u4f46\u540c\u65f6\u4f18\u5316\u65e9\u671f\u8bd5\u9a8c\u8bbe\u8ba1\u5e76\u786e\u4fdd\u60a3\u8005\u5b89\u5168\u4ecd\u662f\u9996\u8981\u4efb\u52a1\u3002\u672c\u7ae0\u8282\u5c06\u8be6\u8ff0\u514d\u75ab\u6cbb\u7597\u65f6\u4ee3\u4e00\u671f\u8bd5\u9a8c\u7684\u7279\u70b9\uff0c\u7279\u522b\u662f\u5bf9\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\u7684\u7814\u7a76\uff0c\u4e3a\u65e9\u671f\u836f\u7269\u5f00\u53d1\u63d0\u4f9b\u91cd\u8981\u7684\u5b9e\u8df5\u6307\u5bfc\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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32.2 \u9488\u5bf9\u514d\u75ab\u68c0\u67e5\u70b9\u7684\u6297\u4f53\u6cbb\u7597<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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32.2.1 \u5242\u91cf\u9650\u5236\u6bd2\u6027\u4e0e\u6700\u5927\u8010\u53d7\u5242\u91cf\uff08MTD\uff09\u7684\u786e\u5b9a<\/p>\n<\/section>\n

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\u5728\u4f20\u7edf\u7684\u836f\u7269\u5f00\u53d1\u4e2d\uff0c\u5e38\u89c4\u7684\u4e00\u671f\u4e34\u5e8a\u8bd5\u9a8c\u8bbe\u8ba1\u9075\u5faa\u201c\u5242\u91cf\u8d8a\u9ad8\u8d8a\u597d\u201d\u7684\u539f\u5219\uff0c\u57fa\u4e8e\u5047\u8bbe\uff1a\u66f4\u9ad8\u5242\u91cf\u7684\u6297\u764c\u836f\u7269\u80fd\u5e26\u6765\u66f4\u4f73\u7597\u6548\uff0c\u54ea\u6015\u9700\u8981\u627f\u53d7\u8f83\u9ad8\u7684\u6bd2\u6027\uff08Fig. 32.1<\/span>\uff09\u3002\u56e0\u6b64\uff0c\u5efa\u7acb\u4e86\u9010\u6b65\u589e\u52a0\u5242\u91cf\u7684\u65b9\u6848\uff0c\u76ee\u7684\u662f\uff1a\uff081\uff09\u9650\u5236\u63a5\u53d7\u4f4e\u5242\u91cf\uff08\u53ef\u80fd\u65e0\u6548\uff09\u6cbb\u7597\u7684\u60a3\u8005\u6570\u91cf\uff0c\uff082\uff09\u901a\u8fc7\u5feb\u901f\u9012\u589e\u5242\u91cf\u4ee5\u7f29\u77ed\u8bd5\u9a8c\u6301\u7eed\u65f6\u95f4\uff0c\uff083\uff09\u5c3d\u53ef\u80fd\u53d1\u73b0\u5e76\u8bc4\u4f30\u53ef\u80fd\u5bf9\u60a3\u8005\u9020\u6210\u4e25\u91cd\u5371\u5bb3\u7684\u6bd2\u6027\uff0c\u4ee5\u6b64\u8c03\u6574\u836f\u7269\u7684\u98ce\u9669\u4e0e\u6536\u76ca\u6bd4\u3002\u8fd9\u79cd\u4e0d\u53ef\u63a5\u53d7\u7684\u6bd2\u6027\u88ab\u79f0\u4e3a\u201c\u5242\u91cf\u9650\u5236\u6bd2\u6027\u201d\uff08DLT\uff09\uff0c\u5b83\u6307\u7684\u662f\u5728\u8d85\u8fc7\u9884\u5b9a\u60a3\u8005\u6570\u91cf\u7684\u60c5\u51b5\u4e0b\u53d1\u751f\u7684\uff0c\u901a\u5e38\u662f\u6cbb\u7597\u7b2c\u4e00\u5468\u671f\uff08\u5373\u524d3\u52304\u5468\uff09\u5185\u51fa\u73b0\u76843\u7ea7\u6216\u4ee5\u4e0a\u7684\u4e25\u91cd\u6bd2\u6027\u3002\u6839\u636e\u7f8e\u56fd\u56fd\u5bb6\u764c\u75c7\u7814\u7a76\u6240\u4e0d\u826f\u4e8b\u4ef6\u901a\u7528\u672f\u8bed\u6807\u51c6\uff08NCI-CTCAE v4.0\uff09\uff0cDLT\u7528\u4e8e\u754c\u5b9a\u6700\u5927\u8010\u53d7\u5242\u91cf\uff08MTD\uff09\u3002\u4f20\u7edf\u7684\u201c3+3\u201d\u5242\u91cf\u9012\u589e\u8bbe\u8ba1\u65e8\u5728\u63a7\u5236DLT\u53d1\u751f\u7387\u572817%-33%\u4e4b\u95f4\uff08\u5373\u6bcf\u516d\u540d\u60a3\u8005\u4e2d\u7ea6\u6709\u4e00\u4eba\u6216\u66f4\u5c11\u4eba\u51fa\u73b0DLT\uff09\uff0c\u4ece\u800c\u786e\u5b9aMTD\u3002\u514d\u75ab\u6cbb\u7597\u9886\u57df\u7684\u53d1\u5c55\u5bf9\u8fd9\u79cd\u4f20\u7edf\u836f\u7269\u5f00\u53d1\u65b9\u6cd5\u63d0\u51fa\u4e86\u65b0\u7684\u6311\u6218\uff0c\u5c24\u5176\u662f\u5728\u9488\u5bf9\u514d\u75ab\u68c0\u67e5\u70b9\u7684\u6297\u4f53\u7814\u7a76\u4e2d\uff08\u8be6\u89c1\u201cChallenges of phase 1 clinical trials evaluating immune checkpoint-targeted antibodies\u201d\u4e00\u6587\uff09\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Fig 32.1<\/span> \u514d\u75ab\u68c0\u67e5\u70b9\u963b\u6ede\u5242\u7684\u5242\u91cf-\u6bd2\u6027\u548c\u5242\u91cf-\u6548\u679c\u5173\u7cfb\u5206\u6790\u3002\u4e0e\u4f20\u7edf\u7684\u7ec6\u80de\u6bd2\u6027\u836f\u7269\uff08\u5982\u5de6\u56fe\u6240\u793a\uff09\u4e0d\u540c\uff0c\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u6ede\u5242\uff08\u5982\u53f3\u56fe\u6240\u793a\uff09\u5e76\u672a\u5c55\u73b0\u51fa\u4efb\u4f55\u7ebf\u6027\u7684\u5242\u91cf-\u6bd2\u6027\u6216\u5242\u91cf-\u6548\u679c\u5173\u7cfb\u3002\u5728\u6240\u6709\u5242\u91cf\u6c34\u5e73\u4e0a\uff0c\u90fd\u53ef\u80fd\u89c2\u5bdf\u5230\u7f55\u89c1\u4f46\u4e25\u91cd\u751a\u81f3\u6709\u65f6\u5a01\u80c1\u751f\u547d\u7684\u514d\u75ab\u76f8\u5173\u4e0d\u826f\u4e8b\u4ef6\uff08irAEs\uff09\u3002\u8fd9\u4e9b\u751f\u7269\u6d3b\u6027\u5242\u7684\u4f5c\u7528\u4e0d\u53d7\u8d85\u8fc7\u6fc0\u53d1\u514d\u75ab\u53cd\u5e94\u6240\u9700\u9608\u503c\u7684\u5242\u91cf\u5f71\u54cd\u3002\u56e0\u6b64\uff0c\u8fd9\u4e9b\u6cbb\u7597\u65b9\u6cd5\u7684\u6cbb\u7597\u7a97\u53e3\u76f8\u6bd4\u4f20\u7edf\u7ec6\u80de\u6bd2\u6027\u836f\u7269\u66f4\u4e3a\u5bbd\u5e7f\u3002\u5728\u56fe\u4e2d\u4f7f\u7528\u989c\u8272\u7f16\u7801\u8868\u793a\u4e0d\u540c\u7a0b\u5ea6\u7684\u6bd2\u6027\uff1a\u8f7b\u5ea6\u6bd2\u6027\u7528\u7eff\u8272\u7ebf\u6761\u8868\u793a\uff0c\u4e2d\u5ea6\u6bd2\u6027\u7528\u6a59\u8272\u7ebf\u6761\u8868\u793a\uff0c\u800c\u91cd\u5ea6\u6bd2\u6027\u5219\u7528\u7ea2\u8272\u7ebf\u6761\u8868\u793a\u3002\u7ea2\u8272\u70b9\u6807\u793a\u51fa\u5728\u514d\u75ab\u7597\u6cd5\u7684\u5242\u91cf\u4f9d\u8d56\u6027\u8f7b\u5ea6\u4e0d\u826f\u4e8b\u4ef6\u8def\u5f84\u4e0a\u53ef\u80fd\u51fa\u73b0\u7684\u4e25\u91cd\u514d\u75ab\u76f8\u5173\u4e0d\u826f\u4e8b\u4ef6\uff08irAEs\uff09\u3002\u6d3b\u52a8\u7a0b\u5ea6\u4ee5\u9ec4\u8272\u8868\u793a\u3002\u56fe\u4e2d\u8fd8\u6807\u6ce8\u4e86\u51e0\u4e2a\u91cd\u8981\u7684\u836f\u7269\u5242\u91cf\u5b9a\u4e49\uff1aDL\u4e3a\u5242\u91cf\u6c34\u5e73\u3001MAD\u4e3a\u6700\u5c0f\u6d3b\u6027\u5242\u91cf\u3001MFD\u4e3a\u6700\u5927\u53ef\u884c\u5242\u91cf\u3001MTD\u4e3a\u6700\u5927\u8010\u53d7\u5242\u91cf\u3001RP2D\u4e3a\u63a8\u8350\u7684\u4e8c\u671f\u5242\u91cf\u3001Ther Index\u4e3a\u6cbb\u7597\u6307\u6570\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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32.2.1.1 \u5b89\u5168\u6027\u548c\u6700\u5927\u8010\u53d7\u5242\u91cf\uff08MTD\uff09\u7684\u5b9a\u4e49<\/p>\n<\/section>\n

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\u514d\u75ab\u7597\u6cd5\u7684\u6bd2\u6027\u8868\u73b0\u4e0e\u4f20\u7edf\u7684\u7ec6\u80de\u6bd2\u6027\u7597\u6cd5\u6216\u9776\u5411\u836f\u7269\u76f8\u6bd4\uff0c\u5728\u591a\u4e2a\u65b9\u9762\u5b58\u5728\u663e\u8457\u5dee\u5f02\u3002\u4f8b\u5982\uff0c\u5728\u8bc4\u4f30\u6297CTLA-4\u836f\u7269\u65f6\uff0c\u5df2\u7ecf\u89c2\u5bdf\u5230\u660e\u786e\u7684\u5242\u91cf-\u6bd2\u6027\u5173\u7cfb\uff0c\u7136\u800c\uff0c\u5728\u5bf9\u6297PD-1\u6216\u6297PD-L1\u836f\u7269\u8fdb\u884c\u7684\u4e00\u671f\u5355\u836f\u6cbb\u7597\u8bd5\u9a8c\u4e2d\uff0c\u5e76\u672a\u53d1\u73b0\u5242\u91cf\u4e0e\u5b89\u5168\u6027\u4e4b\u95f4\u6709\u660e\u663e\u7684\u76f8\u5173\u6027\uff0c\u8fd9\u4e00\u70b9\u5728\u540e\u7eed\u7684\u7814\u7a76\u4e2d\u4e5f\u5f97\u5230\u4e86\u8bc1\u5b9e\u3002\u4ee5\u7eb3\u6b66\u5229\u5c24\u5355\u6297\uff08Opdivo\u00ae, \u767e\u65f6\u7f8e\u65bd\u8d35\u5b9d\uff09\u4e3a\u4f8b\uff0c\u5176\u7597\u6548\u548c\u5b89\u5168\u6027\u5728\u6bcf2\u5468\u6216\u6bcf3\u5468\u7ed9\u836f2\u81f320 mg\/kg\u7684\u5242\u91cf\u8303\u56f4\u5185\u8868\u73b0\u51fa\u76f8\u5bf9\u7a33\u5b9a\u6027\u3002\u6b64\u5916\uff0c\u5728\u5bf913\u4e2a\u4e3b\u8981\u9488\u5bf9\u6297CTLA-4\u3001\u6297PD-1\u6216\u6297PD-L1\u836f\u7269\u7684\u4e00\u671f\u5355\u836f\u6cbb\u7597\u8bd5\u9a8c\u7684\u8003\u5bdf\u4e2d\uff0c\u4ec5\u6709\u4e00\u9879\u8bd5\u9a8c\u6839\u636e\u534f\u8bae\u5b9a\u4e49\u4e86\u5242\u91cf\u9650\u5236\u6bd2\u6027\uff08DLT\uff09\uff0c\u800c\u51e0\u4e4e\u6240\u6709\u8bd5\u9a8c\u90fd\u672a\u80fd\u786e\u5b9a\u6700\u5927\u8010\u53d7\u5242\u91cf\uff08MTD\uff09\u3002\u56e0\u6b64\uff0c\u901a\u5e38\u5efa\u8bae\u7684\u7b2c\u4e8c\u9636\u6bb5\u5242\u91cf\uff08RP2D\uff09\u5f80\u5f80\u88ab\u5b9a\u4e3a\u6700\u5927\u53ef\u884c\u5242\u91cf\uff08MFD\uff09\uff0c\u800c\u4e0d\u662f\u57fa\u4e8e\u5b89\u5168\u6027\u6570\u636e\u786e\u5b9a\u3002\u503c\u5f97\u6ce8\u610f\u7684\u662f\uff0c\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u7684\u63a8\u8350\u5242\u91cf\u662f\u57fa\u4e8e\u4e00\u9879\u5927\u578b1b\u671f\u7814\u7a76\uff0c\u901a\u8fc7\u7efc\u5408\u836f\u4ee3\u52a8\u529b\u5b66\uff08PK\uff0c\u53cd\u6620\u836f\u7269\u66b4\u9732\uff09\u3001\u836f\u6548\u5b66\uff08PD\uff09\u3001\u5b89\u5168\u6027\u548c\u6709\u6548\u6027\u6570\u636e\u6765\u786e\u5b9a\u7684\u3002\u4e0e\u9776\u5411\u6cbb\u7597\u76f8\u4f3c\uff0c\u5927\u591a\u6570\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u6ede\u5242\u6700\u7ec8\u91c7\u7528\u56fa\u5b9a\u5242\u91cf\u7ed9\u836f\uff0c\u4e0d\u6839\u636e\u4f53\u91cd\u3001\u4f53\u8868\u9762\u79ef\u6216\u4efb\u4f55\u60a3\u8005\u7279\u5b9a\u53c2\u6570\u8fdb\u884c\u8c03\u6574\uff08Fig 32.1<\/span>\uff09\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5728\u8ba8\u8bba\u662f\u5426\u5b58\u5728\u5242\u91cf\u9650\u5236\u6bd2\u6027\uff08DLT\uff09\u6216\u6700\u5927\u8010\u53d7\u5242\u91cf\uff08MTD\uff09\u65f6\uff0c\u4e0d\u80fd\u7b80\u5355\u5730\u8ba4\u4e3a\u8fd9\u4e9b\u7597\u6cd5\u65e0\u6bd2\u6027\u3002\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u6ede\u5242\u5f15\u8d77\u7684\u4e25\u91cd\u6bd2\u6027\u786e\u5b9e\u901a\u5e38\u4f4e\u4e8e\u7ec6\u80de\u6bd2\u6027\u6216\u9776\u5411\u7597\u6cd5\uff0c\u4f46DLT\u7684\u7f3a\u5931\u4e3b\u8981\u5f52\u56e0\u4e8e\u6bd2\u6027\u7684\u4e0d\u540c\u52a8\u529b\u5b66\u7279\u5f81\u3002DLT\u901a\u5e38\u53ea\u5728\u6cbb\u7597\u7684\u7b2c\u4e00\u4e2a\u5468\u671f\u8bc4\u4f30\uff0c\u8fd9\u671f\u95f4\u89c2\u5bdf\u5230\u7684\u6bd2\u6027\u76f4\u63a5\u5173\u8054\u4e8e\u836f\u7269\u5bf9\u5065\u5eb7\u7ec6\u80de\u7684\u6025\u6027\u5f71\u54cd\u3002\u76f8\u8f83\u4e4b\u4e0b\uff0c\u514d\u75ab\u7597\u6cd5\u5f15\u53d1\u7684\u6bd2\u6027\u5f80\u5f80\u662f\u95f4\u63a5\u7684\uff1a\u4e3b\u8981\u662f\u7531\u4e8e\u514d\u75ab\u7cfb\u7edf\u5bf9\u836f\u7269\u7684\u4e0d\u5145\u5206\u6216\u4e0d\u9002\u5f53\u53cd\u5e94\u6240\u81f4\uff0c\u53ef\u80fd\u662f\u53cd\u5e94\u7684\u6027\u8d28\u6216\u5f3a\u5ea6\u4e0d\u8db3\uff0c\u6216\u662f\u514d\u75ab\u7ec6\u80de\u54cd\u5e94\u7684\u518d\u7f16\u7a0b\u4e0d\u5f53\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u8fd9\u79cd\u533a\u522b\u5bfc\u81f4\u4e86\u4e0d\u826f\u4e8b\u4ef6\uff08AEs\uff09\u4e0e\u514d\u75ab\u76f8\u5173\u4e0d\u826f\u4e8b\u4ef6\uff08irAEs\uff09\u4e4b\u95f4\u7684\u5dee\u5f02\u3002irAEs\u901a\u5e38\u6709\u4e00\u6bb5\u5fc5\u8981\u7684\u6f5c\u4f0f\u671f\uff0c\u8fd9\u4e2a\u6f5c\u4f0f\u671f\u968f\u836f\u7269\u7684\u6027\u8d28\u800c\u5f02\uff0c\u5982ipilimumab\u5927\u7ea6\u4e3a8\u81f310\u5468\u3002\u56e0\u6b64\uff0c\u4ec5\u9650\u4e8e\u7b2c\u4e00\u4e2a\u5468\u671f\u7684DLT\u65e0\u6cd5\u5145\u5206\u6355\u6349\u5230\u8fd9\u4e9b\u4e0e\u836f\u7269\u76f8\u5173\u7684\u6f5c\u5728\u6bd2\u6027\uff0c\u4e14\u5728\u5242\u91cf\u589e\u52a0\u8fc7\u7a0b\u4e2d\u8fd9\u4e9b\u6bd2\u6027\u672a\u88ab\u5145\u5206\u8003\u8651\u3002\u8003\u8651\u5230\u5242\u91cf-\u6bd2\u6027\u5173\u7cfb\u7ecf\u5e38\u7f3a\u5931\u548c\u4e00\u671f\u8bd5\u9a8c\u7684\u8fc5\u901f\u5b8c\u6210\u7684\u5fc5\u8981\u6027\uff0c\u8fd9\u79cd\u665a\u53d1\u6027\u6bd2\u6027\u5e94\u5728\u4e00\u671f\u7814\u7a76\u4e2d\u8be6\u7ec6\u62a5\u544a\u5e76\u6307\u660e\u5176\u53d1\u751f\u5468\u671f\u3002\u4f8b\u5982\uff0c\u5728\u8bc4\u4f30\u6297PD-L1\u836f\u7269\u5982BMS-936559\u548cdurvalumab\uff08\u963f\u65af\u5229\u5eb7\uff09\u7684\u4e00\u671f\u8bd5\u9a8c\u4e2d\uff0c\u7814\u7a76\u8005\u5df2\u7ecf\u9009\u62e9\u5c06DLT\u8bc4\u4f30\u5468\u671f\u5ef6\u957f\u81f3\u4e24\u4e2a\u5468\u671f\uff0c\u4ee5\u66f4\u597d\u5730\u8003\u8651\u514d\u75ab\u76f8\u5173\u7684\u6bd2\u6027\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u5728\u8bc4\u4f30\u514d\u75ab\u7597\u6cd5\u7684\u4e00\u671f\u8bd5\u9a8c\u4e2d\uff0cDLT\u53ef\u80fd\u4e0d\u4ec5\u5c40\u9650\u4e8e\u4e25\u91cd\u6bd2\u6027\uff08NCI-CTCAE 3\u7ea7\u4ee5\u4e0a\uff09\u3002\u4e8b\u5b9e\u4e0a\uff0c\u5728\u66f4\u4e25\u91cd\u7684\u60c5\u51b5\u4e0b\uff0cirAEs\u9700\u8981\u8fc5\u901f\u4e14\u7279\u5b9a\u7684\u6cbb\u7597\uff0c\u4e3b\u8981\u4f9d\u8d56\u514d\u75ab\u6291\u5236\u548c\u6297\u708e\u836f\u7269\uff0c\u5982\u7c7b\u56fa\u9187\u3001\u6297TNF\u6216\u6297IL-6\u836f\u7269\u3002\u56e0\u6b64\uff0c\u5927\u591a\u6570\u8bd5\u9a8c\u73b0\u5728\u5efa\u8bae\uff0c\u4e00\u65e6\u89c2\u5bdf\u5230\u4e2d\u5ea6\uff082\u7ea7\uff09irAEs\uff0c\u5e94\u7acb\u5373\u505c\u6b62\u7ed9\u836f\uff0c\u5e76\u6839\u636e\u4e13\u7528\u6307\u5357\u5f00\u59cb\u8fc5\u901f\u6cbb\u7597\u5e72\u9884\u3002\u5c3d\u7ba1\u5728\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u6ede\u5242\u7684\u836f\u4ee3\u52a8\u529b\u5b66\u65b9\u9762\u4ecd\u5b58\u5728\u4e00\u4e9b\u4e0d\u786e\u5b9a\u6027\uff0c\u4f46\u836f\u7269\u4e2d\u65ad\u53ef\u80fd\u5bfc\u81f4\u836f\u7269\u66b4\u9732\u51cf\u5c11\uff0c\u6839\u636e\u6700\u65b0\u7684\u5efa\u8bae\uff0c\u8fd9\u5e94\u88ab\u8bc4\u5b9a\u4e3aDLT\u3002\u6700\u91cd\u8981\u7684\u662f\uff0c\u8fd9\u79cd\u5ef6\u8fdf\u6027\u6bd2\u6027\u5e94\u5728\u5242\u91cf\u63a8\u8350\u8fc7\u7a0b\u4ee5\u53ca\u6bd2\u6027\u7ba1\u7406\u6307\u5357\u7684\u5236\u5b9a\u4e2d\u5f97\u5230\u7279\u522b\u8003\u8651\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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32.2.1.2 \u5242\u91cf\u65f6\u95f4\u8868<\/p>\n<\/section>\n

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\u5728\u514d\u75ab\u6cbb\u7597\u9886\u57df\uff0c\u591a\u6570\u60c5\u51b5\u4e0b\u5e76\u672a\u89c2\u5bdf\u5230\u660e\u663e\u7684\u7ebf\u6027\u5242\u91cf-\u53cd\u5e94\u5173\u7cfb\uff08Fig 32.1<\/span>\uff09\u3002\u4f8b\u5982\uff0c\u9488\u5bf9\u591a\u4e2a\u5242\u91cf\u6c34\u5e73\u7684nivolumab\u4e00\u671f\u8bd5\u9a8c\u4e2d\uff0c\u6d3b\u6027\u5728\u6240\u6709\u5242\u91cf\u7ea7\u522b\u4e0a\u5747\u6709\u89c2\u5bdf\u5230\uff1b\u7c7b\u4f3c\u5730\uff0c\u5728\u8f6c\u79fb\u6027\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u4e2d\uff0c\u9ad8\u5242\u91cf\u7684\u6297CTLA-4\u836f\u7269\uff0c\u5982ipilimumab\u548ctremelimumab\uff0c\u5e76\u672a\u5c55\u793a\u51fa\u66f4\u9ad8\u7684\u7f13\u89e3\u7387\u3002\u751a\u81f3\u5728\u4e00\u9879\u63a2\u7d22\u4e09\u79cd\u4e0d\u540c\u5242\u91cfipilimumab\u7684\u4e8c\u671f\u8bd5\u9a8c\u4e2d\u63d0\u51fa\u7684\u5242\u91cf\u54cd\u5e94\uff0c\u5728\u66f4\u5927\u89c4\u6a21\u7684\u4e09\u671f\u8bd5\u9a8c\u4e2d\u4e5f\u672a\u80fd\u5f97\u5230\u8bc1\u5b9e\u3002\u56e0\u6b64\uff0c\u8ffd\u6c42\u6700\u9ad8\u53ef\u8010\u53d7\u5242\u91cf\u5bf9\u8fd9\u4e9b\u836f\u7269\u6765\u8bf4\u53ef\u80fd\u65e0\u5173\u7d27\u8981\uff0c\u800c\u5e94\u8003\u8651\u5b83\u4eec\u5728\u8f83\u4f4e\u5242\u91cf\u6c34\u5e73\u7684\u6f5c\u5728\u7597\u6548\u3002\u5728\u8fd9\u79cd\u80cc\u666f\u4e0b\uff0c\u5e94\u91c7\u7528\u7cfb\u7edf\u7684\u521b\u65b0\u8bbe\u8ba1\uff0c\u5141\u8bb8\u5242\u91cf\u8fc5\u901f\u63d0\u9ad8\uff08\u4f8b\u5982\u91c7\u7528\u52a0\u901f\u6ef4\u5b9a\u8bbe\u8ba1\u6216\u4fee\u6539\u7684\u6bd2\u6027\u6982\u7387\u533a\u95f4\u8bbe\u8ba1\uff09\uff0c\u5e76\u5728\u786e\u5b9a\u6ee1\u610f\u7684\u836f\u4ee3\u52a8\u529b\u5b66\u548c\u836f\u6548\u5b66\u53c2\u6570\u540e\uff0c\u7acb\u5373\u5728\u4f4e\u5242\u91cf\u6c34\u5e73\u8fdb\u884c\u6269\u5c55\uff08Fig 32.2<\/span>\uff09\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u9664\u4e86\u5242\u91cf\u95ee\u9898\u5916\uff0c\u6700\u4f73\u7ed9\u836f\u65f6\u95f4\u8868\u4e5f\u5b58\u5728\u4e89\u8bae\u3002\u5c3d\u7ba1\u5f53\u524d\u5927\u591a\u6570\u5355\u514b\u9686\u6297\u4f53\u7684\u7ed9\u836f\u9891\u7387\u4e3a\u6bcf2\u62163\u5468\u4e00\u6b21\uff0c\u4f46\u6839\u636e\u6297\u4f53\u7684\u540c\u578b\uff0c\u672a\u80fd\u53d1\u73b0\u4e00\u81f4\u7684\u6a21\u5f0f\u3002\u8fd8\u6709\u4e00\u4e9b\u5f85\u63a2\u7d22\u7684\u672a\u77e5\u56e0\u7d20\uff0c\u5982\u6297\u4f53\u5bf9\u5176\u9776\u6807\u7684\u6e05\u9664\u673a\u5236\u3002\u4e00\u671f\u4e34\u5e8a\u8bd5\u9a8c\u5e94\u81f4\u529b\u4e8e\u6df1\u5165\u63a2\u7d22\u8fd9\u4e9b\u95ee\u9898\uff08\u8be6\u89c1\u836f\u4ee3\u52a8\u529b\u5b66\u548c\u836f\u6548\u5b66\u53c2\u6570\u90e8\u5206\uff09\u3002\u4f8b\u5982\uff0c\u76ee\u524d\u6297PD-1\u548c\u6297PD-L1\u836f\u7269\u662f\u6309\u8fde\u7eed\u65b9\u6848\u5355\u836f\u6cbb\u7597\u5b9e\u65bd\u7684\uff0c\u800c\u6297CTLA-4\u836f\u7269ipilimumab\u5df2\u88ab\u6279\u51c6\u4ee53 mg\/kg\u5242\u91cf\uff0c\u6bcf3\u5468\u4e00\u6b21\uff0c\u5171\u7ed9\u4e884\u5242\u3002\u6709\u7814\u7a76\u5728\u8bc4\u4f30\u8f83\u4f4e\u5242\u91cf\u7ef4\u6301\u6cbb\u7597\u7684\u6f5c\u529b\u3002\u5bf9\u4e8e\u90a3\u4e9b\u5728\u505c\u6b62\u6cbb\u7597\u540e\u4ecd\u663e\u793a\u6301\u7eed\u80bf\u7624\u53cd\u5e94\u4f46\u6700\u7ec8\u590d\u53d1\u7684\u60a3\u8005\uff0c\u6709\u6548\u7684\u518d\u8bf1\u5bfc\u6cbb\u7597\u6f5c\u529b\u4e5f\u5e94\u8be5\u88ab\u7cfb\u7edf\u8003\u8651\u3002\u7136\u800c\uff0c\u867d\u7136\u4e00\u671f\u8bd5\u9a8c\u662f\u6d4b\u8bd5\u8fd9\u4e9b\u65b9\u6848\u7684\u53ef\u884c\u6027\u548c\u5b89\u5168\u6027\u7684\u5e73\u53f0\uff0c\u771f\u6b63\u7684\u7597\u6548\u6bd4\u8f83\u5219\u9700\u8981\u5728\u540e\u671f\u8bd5\u9a8c\u4e2d\uff0c\u9488\u5bf9\u7279\u5b9a\u80bf\u7624\u7c7b\u578b\u8fdb\u884c\u6709\u76ee\u7684\u7684\u8be6\u7ec6\u8bc4\u4f30\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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Fig. 32.2 <\/span>\u514d\u75ab\u80bf\u7624\u5b66\u65f6\u4ee3\u7684\u65b0\u4e00\u671f\u8bd5\u9a8c\u8bbe\u8ba1\u3002\u4f20\u7edf\u7684\u836f\u7269\u5f00\u53d1\u6d41\u7a0b\uff08\u5982\u9876\u90e8\u9762\u677f\u6240\u793a\uff09\u901a\u5e38\u5305\u62ec\u4e09\u4e2a\u72ec\u7acb\u7684\u9636\u6bb5\uff1a\u4e00\u671f\u3001\u4e8c\u671f\u548c\u4e09\u671f\u7814\u7a76\uff08\u4ee5\u592a\u9633\u5f62\u72b6\u7684\u201cA\u201d\u6807\u8bc6\uff09\u3002\u4f20\u7edf\u7684\u4e00\u671f\u8bd5\u9a8c\u521d\u671f\u4e3a\u5242\u91cf\u9012\u589e\u9636\u6bb5\uff0c\u968f\u540e\u662f\u5355\u4e00\u961f\u5217\u7684\u5242\u91cf\u6269\u5c55\u9636\u6bb5\uff0c\u4e3b\u8981\u76ee\u7684\u662f\u8bc4\u4f30\u5b89\u5168\u6027\u5e76\u786e\u5b9a\u63a8\u8350\u7684\u4e8c\u671f\u5242\u91cf\u3002\u5728\u6570\u636e\u652f\u6301\u521d\u6b65\u7597\u6548\u7684\u57fa\u7840\u4e0a\uff0c\u7ea6\u4e09\u5e74\u7684\u4e00\u671f\u8bd5\u9a8c\u901a\u5e38\u4f1a\u8fdb\u5165\u540e\u7eed\u7684\u4e8c\u671f\u548c\u4e09\u671f\u8bd5\u9a8c\uff0c\u6574\u4e2a\u836f\u7269\u5f00\u53d1\u5468\u671f\u901a\u5e38\u8d85\u8fc710\u5e74\u3002\u65b0\u7684\u836f\u7269\u5f00\u53d1\u6a21\u5f0f\u5f15\u5165\u4e86\u201c\u6ce8\u518c\u5bfc\u5411\u7684\u4e00\u671f\u8bd5\u9a8c\u201d\uff0c\u5728\u8fd9\u7c7b\u8bd5\u9a8c\u4e2d\uff0c\u6269\u5c55\u961f\u5217\u4e0d\u4ec5\u5173\u6ce8\u5b89\u5168\u6027\uff0c\u8fd8\u5728\u5177\u6709\u5145\u5206\u7edf\u8ba1\u52a8\u529b\u7684\u7279\u5b9a\u75be\u75c5\u961f\u5217\u4e2d\u63a2\u7d22\u836f\u7269\u7684\u6d3b\u6027\u3002\u6b64\u5916\uff0c\u591a\u4e2a\u8054\u5408\u7597\u6cd5\u961f\u5217\u53ef\u4ee5\u4f5c\u4e3a\u521d\u671f\u4e00\u671f\u8bd5\u9a8c\u7684\u4e00\u90e8\u5206\uff0c\u5e76\u5728\u9002\u5f53\u7684\u65b9\u6848\u4fee\u8ba2\u540e\u8fdb\u884c\uff0c\u4ee5\u8bc4\u4f30\u4e0d\u540c\u836f\u7269\u7ec4\u5408\u7684\u5b89\u5168\u6027\u548c\u521d\u6b65\u7597\u6548\u3002\u8fd9\u4e9b\u5e76\u884c\u7684\u591a\u961f\u5217\u8bd5\u9a8c\u53ef\u80fd\u6db5\u76d6\u6570\u767e\u540d\u60a3\u8005\uff0c\u53ef\u80fd\u5bfc\u81f4\u836f\u7269\u83b7\u5f97\u7a81\u7834\u6027\u6307\u5b9a\u3001\u6761\u4ef6\u6279\u51c6\u6216\u52a0\u901f\u6279\u51c6\uff0c\u4ece\u800c\u663e\u8457\u7f29\u77ed\u6574\u4f53\u7684\u836f\u7269\u5f00\u53d1\u65f6\u95f4\u3002\u7279\u5b9a\u60a3\u8005\u961f\u5217\u4e5f\u53ef\u4ee5\u5f00\u653e\uff0c\u4ee5\u4fbf\u8bc4\u4f30\u836f\u7269\u5728\u5b58\u5728\u7279\u5b9a\u5408\u5e76\u75c7\u7684\u60a3\u8005\u7fa4\u4e2d\u7684\u5b89\u5168\u6027\u3002\u540c\u65f6\uff0c\u5176\u4ed6\u60a3\u8005\u53ef\u4ee5\u52a0\u5165\u5df2\u8bc1\u660e\u5b89\u5168\u4e14\u9ad8\u4e8e\u6700\u5c0f\u6d3b\u6027\u5242\u91cf\u7684\u5242\u91cf\u9012\u589e\u9636\u6bb5\u3002\u8fd9\u5141\u8bb8\u5728\u591a\u4e2a\u5242\u91cf\u6c34\u5e73\u4e0a\u4e30\u5bcc\u5b89\u5168\u6027\u3001\u836f\u4ee3\u52a8\u529b\u5b66\uff08PK\uff09\u3001\u836f\u6548\u5b66\uff08PD\uff09\u53ca\u7597\u6548\u6570\u636e\uff0c\u589e\u52a0\u53ef\u80fd\u4ece\u836f\u7269\u6cbb\u7597\u4e2d\u53d7\u76ca\u7684\u60a3\u8005\u6570\u91cf\uff0c\u800c\u4e0d\u4f1a\u5ef6\u8bef\u5242\u91cf\u9012\u589e\u8fc7\u7a0b\u3002\u8fd9\u91cc\u7684\u5173\u952e\u672f\u8bed\u5305\u62ec\u6700\u5c0f\u6709\u6548\u5242\u91cf\uff08MAD\uff09\u3001\u6700\u5927\u53ef\u884c\u5242\u91cf\uff08MFD\uff09\u3001\u6700\u5927\u8010\u53d7\u5242\u91cf\uff08MTD\uff09\u3001\u63a8\u8350\u4e8c\u671f\u5242\u91cf\uff08RP2D\uff09\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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32.2.2  \u5b89\u5168\u6027\u4e0e\u6bd2\u6027\u7ba1\u7406<\/p>\n<\/section>\n

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\u672c\u4e66\u4e2d\u6709\u4e00\u6574\u7ae0\u8be6\u7ec6\u8ba8\u8bba\u4e86\u514d\u75ab\u80bf\u7624\u5b66\uff08I-O\uff09\u7684\u526f\u4f5c\u7528\uff0c\u8fd9\u91cc\u6211\u4eec\u5c06\u6982\u8ff0\u4e00\u671f\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u7684\u5173\u952e\u6982\u5ff5\u548c\u5386\u53f2\u8fdb\u5c55\u3002<\/p>\n

\u5728\u4e00\u671f\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\uff0c\u9700\u8981\u7279\u522b\u5173\u6ce8\u514d\u75ab\u6bd2\u6027\uff08\u514d\u75ab\u76f8\u5173\u4e0d\u826f\u4e8b\u4ef6\uff0cirAEs\uff09\u7684\u51e0\u4e2a\u7279\u70b9\uff08Fig. 32.3<\/span>\uff09\u3002\u9996\u5148\uff0cirAEs\u53ef\u80fd\u5f71\u54cd\u4efb\u4f55\u5668\u5b98\uff0c\u867d\u7136\u6297CTLA-4\u548c\u6297PD-1\/PD-L1\u836f\u7269\u7684\u65e9\u671f\u8bd5\u9a8c\u4e3b\u8981\u5173\u6ce8\u7ed3\u80a0\u708e\u548c\u80ba\u708e\uff0c\u4f46\u5b9e\u9645\u4e0a\uff0c\u4efb\u4f55\u5668\u5b98\u7684irAEs\u90fd\u5e94\u5728\u75c5\u5386\u4e2d\u88ab\u4ed4\u7ec6\u4e14\u8be6\u5c3d\u5730\u8bb0\u5f55\u3002\u5176\u6b21\uff0cirAEs\u867d\u7136\u53d1\u751f\u7387\u4e0d\u9ad8\uff0c\u4f46\u53ef\u80fd\u8fc5\u901f\u6076\u5316\u5e76\u5e26\u6765\u751f\u547d\u5371\u9669\uff0c\u56e0\u6b64\u5fc5\u987b\u6559\u80b2\u60a3\u8005\u53ca\u65f6\u62a5\u544a\u4efb\u4f55\u75c7\u72b6\uff0c\u907f\u514d\u5ef6\u8bef\u6216\u81ea\u884c\u5904\u7406\u3002\u7b2c\u4e09\uff0c\u9274\u4e8eirAEs\u7684\u7279\u6b8a\u7ba1\u7406\u9700\u6c42\uff0c\u4e00\u671f\u8bd5\u9a8c\u65b9\u6848\u4e2d\u5e94\u5305\u542b\u660e\u786e\u7684\u6bd2\u6027\u7ba1\u7406\u6307\u5357\uff0c\u5e76\u8981\u6c42\u4e00\u65e6irAEs\u8fbe\u52302\u7ea7\uff0c\u60a3\u8005\u5e94\u7acb\u5373\u7531\u76f8\u5173\u5668\u5b98\u7684\u4e13\u5bb6\u8fdb\u884c\u5904\u7406\u3002\u7406\u60f3\u60c5\u51b5\u4e0b\uff0c\u4e00\u671f\u8bd5\u9a8c\u5355\u4f4d\u5e94\u4e0e\u5668\u5b98\u4e13\u5bb6\u5efa\u7acb\u5408\u4f5c\u7f51\u7edc\uff0c\u4ee5\u4f18\u5316irAEs\u7684\u8bc6\u522b\u548c\u7ba1\u7406\u3002\u8fd9\u4e0d\u4ec5\u6709\u52a9\u4e8e\u4f18\u5316\u6cbb\u7597\uff0c\u8fd8\u53ef\u4ee5\u5728\u5e94\u7528\u4efb\u4f55\u514d\u75ab\u6291\u5236\u5242\u4e4b\u524d\uff0c\u4ece\u7ecf\u5386\u6bd2\u6027\u53cd\u5e94\u7684\u60a3\u8005\u90a3\u91cc\u6536\u96c6\u7ec4\u7ec7\u6216\u8840\u6db2\u6837\u672c\uff0c\u8fdb\u884c\u751f\u7406\u75c5\u7406\u7814\u7a76\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

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Fig.32.3 <\/span>\u5728\u4e00\u671f\u8bd5\u9a8c\u4e2d\uff0c\u9488\u5bf9\u514d\u75ab\u76f8\u5173\u4e0d\u826f\u4e8b\u4ef6\uff08irAEs\uff09\u7684\u7279\u6b8a\u6027\u9700\u8981\u7279\u522b\u5173\u6ce8\u3002\u8fd9\u4e9b\u4e0d\u826f\u4e8b\u4ef6\u53ef\u80fd\u662f\u591a\u53d8\u4e14\u4e0d\u53ef\u9884\u77e5\u7684\uff0c\u4f46\u5982\u679c\u7ba1\u7406\u5f97\u5f53\uff0c\u5f80\u5f80\u662f\u53ef\u9006\u7684\u3002\u5173\u952e\u5728\u4e8e\u8fdb\u884c\u6df1\u5165\u7684\u751f\u7406\u75c5\u7406\u5b66\u63a2\u7d22\uff0c\u5305\u62ec\u5fc5\u8981\u65f6\u8fdb\u884c\u6d3b\u7ec4\u7ec7\u68c0\u67e5\u548c\u53d6\u6837\u3002<\/span>irAEs\u53ef\u80fd\u5177\u6709\u6f5c\u5728\u7684\u751f\u547d\u5a01\u80c1\u6027\uff0c\u56e0\u6b64\u5728\u51fa\u73b0\u4e25\u91cd\u4e8b\u4ef6\u65f6\uff0c\u786e\u4fdd\u80fd\u8fc5\u901f\u8fdb\u5165\u91cd\u75c7\u76d1\u62a4\u5ba4\uff08ICU\uff09\u81f3\u5173\u91cd\u8981\u3002\u6b64\u5916\uff0c\u8fd9\u4e9b\u4e0d\u826f\u4e8b\u4ef6\u7684\u7ba1\u7406\u9700\u8981\u7279\u5b9a\u7684\u63aa\u65bd\uff0c\u5e76\u4f9d\u8d56\u4e8e\u5168\u79d1\u533b\u751f\uff08GPs\uff09\u3001\u91cd\u75c7\u76d1\u62a4\u4e13\u5bb6\u548c\u76f8\u5173\u533b\u7597\u56e2\u961f\u7684\u7d27\u5bc6\u5408\u4f5c\u3002<\/span>\u4e3a\u4e86\u6709\u6548\u7ba1\u7406\u548c\u5feb\u901f\u54cd\u5e94\uff0c\u5efa\u7acb\u4f18\u5316\u7684\u6570\u636e\u5171\u4eab\u7cfb\u7edf\u975e\u5e38\u91cd\u8981\uff0c\u8fd9\u5305\u62ec\u7535\u8bdd\u4f1a\u8bae\uff08TC\uff09\u548c\u90ae\u4ef6\u63d0\u9192\u7cfb\u7edf\uff0c\u4ee5\u786e\u4fdd\u6240\u6709\u5173\u952e\u4fe1\u606f\u53ca\u65f6\u4f20\u8fbe\u3002\u6b64\u5916\uff0c\u5e94\u5236\u5b9a\u534f\u4f5c\u6027\u7684\u6cbb\u7597\u6307\u5357\uff0c\u660e\u786e\u6bcf\u4e00\u6b65\u7684\u7ba1\u7406\u7b56\u7565\uff0c\u5305\u62ec\u5728\u4e0d\u540c\u60c5\u51b5\u4e0b\u7684\u5177\u4f53\u5e72\u9884\u63aa\u65bd\u3002<\/span>\u901a\u77e5\u548c\u6559\u80b2\u60a3\u8005\u53ca\u5176\u5168\u79d1\u533b\u751f\u5173\u4e8e\u53ef\u80fd\u9047\u5230\u7684irAEs\u53ca\u5176\u53d8\u5316\u6027\u662f\u5fc5\u8981\u7684\u3002\u901a\u8fc7\u8fd9\u79cd\u65b9\u5f0f\uff0c\u53ef\u4ee5\u63d0\u5347\u60a3\u8005\u53ca\u533b\u7597\u63d0\u4f9b\u8005\u5bf9\u8fd9\u4e9b\u4e8b\u4ef6\u7684\u8ba4\u8bc6\u548c\u5e94\u5bf9\u80fd\u529b\uff0c\u4ece\u800c\u6709\u6548\u5730\u964d\u4f4e\u98ce\u9669\u5e76\u4f18\u5316\u6cbb\u7597\u6210\u679c\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6b64\u5916\uff0c\u6709\u5173\u4e25\u91cd\u6bd2\u6027\u4e8b\u4ef6\u7684\u5386\u53f2\u6848\u4f8b\u63d0\u4f9b\u4e86\u91cd\u8981\u7684\u6559\u8bad\uff0c\u4f8b\u5982\u4e00\u79cd\u9488\u5bf9\u514d\u75ab\u7a81\u89e6\u7684\u6cbb\u7597\u65b9\u6cd5\uff0c\u7531\u4e8e\u8d77\u59cb\u5242\u91cf\u9009\u62e9\u4e0d\u5f53\u800c\u5bfc\u81f4\u7684\u4e25\u91cd\u4e0d\u826f\u53cd\u5e94\u3002\u8fd9\u4e2a\u4e8b\u4ef6\u8bf4\u660e\uff0c\u8d77\u59cb\u5242\u91cf\u5e94\u57fa\u4e8e\u6700\u5c0f\u751f\u7269\u6548\u5e94\u6c34\u5e73\uff08MABEL\uff09\u800c\u975e\u4f20\u7edf\u7684\u672a\u89c2\u5bdf\u5230\u4e0d\u826f\u53cd\u5e94\u6c34\u5e73\uff08NOAEL\uff09\uff0c\u5e76\u9700\u8003\u8651\u4eba\u7c7b\u4e0e\u52a8\u7269\uff08\u5305\u62ec\u5c0f\u9f20\u548c\u7315\u7334\uff09\u514d\u75ab\u7cfb\u7edf\u95f4\u7684\u5dee\u5f02\u3002\u8fd9\u79cd\u4e25\u91cd\u7684\u6bd2\u6027\u53cd\u5e94\u4f7f\u5f97\u76f8\u5173\u6cbb\u7597\u65b9\u6cd5\u7684\u53d1\u5c55\u6570\u5e74\u5904\u4e8e\u505c\u6ede\u3002\u8fd9\u4e00\u6848\u4f8b\uff0c\u8fde\u540c\u5176\u4ed6\u75ab\u82d7\u548cCAR-T\u7ec6\u80de\u6cbb\u7597\u7684\u8ba8\u8bba\uff0c\u51f8\u663e\u4e86I-O\u836f\u7269\u6bd2\u6027\u7684\u4e0d\u53ef\u9884\u6d4b\u6027\uff0c\u5b83\u4eec\u867d\u7136\u7f55\u89c1\u4f46\u901a\u5e38\u4e25\u91cd\uff0c\u5e76\u9700\u8981\u5728\u4e13\u4e1a\u5355\u4f4d\u8fdb\u884c\u53ca\u65f6\u4e14\u5177\u4f53\u7684\u7ba1\u7406\u3002\u56e0\u6b64\uff0c\u5bf9\u4e8e\u9996\u521b\u6216\u9996\u6b21\u7528\u4e8e\u4eba\u4f53\u7684\u836f\u7269\uff0c\u514d\u75ab\u7597\u6cd5\u7684\u4e00\u671f\u8bd5\u9a8c\u81f3\u5c11\u5e94\u5728\u5177\u5907\u4e30\u5bcc\u7ecf\u9a8c\u7684\u5927\u578b\u4e00\u671f\u4e2d\u5fc3\u8fdb\u884c\uff0c\u8fd9\u4e9b\u4e2d\u5fc3\u80fd\u591f\u7acb\u5373\u63d0\u4f9b\u91cd\u75c7\u76d1\u62a4\u548c\u6709\u6548\u7684\u514d\u75ab\u6291\u5236\u6cbb\u7597\uff08\u5305\u62ec\u6297TNF\u548c\u6297IL-6\u836f\u7269\uff09\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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32.2.3 \u836f\u4ee3\u52a8\u529b\u5b66\u548c\u836f\u6548\u5b66\u8bc4\u4ef7<\/p>\n<\/section>\n

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32.2.3.1  \u836f\u4ee3\u52a8\u529b\u5b66<\/p>\n<\/section>\n

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\u4e0e\u6b64\u76f8\u6bd4\uff0c\u7f3a\u4e4fFc\u533a\u57df\u7684\u53cc\u7279\u5f02\u6027\u6297\u4f53\u901a\u5e38\u5177\u6709\u975e\u5e38\u77ed\u7684\u534a\u8870\u671f\uff0c\u8fd9\u5bf9\u4e8e\u7ba1\u7406\u836f\u7269\u4e0d\u826f\u53cd\u5e94\uff08\u4f8b\u5982\u7ec6\u80de\u56e0\u5b50\u91ca\u653e\u7efc\u5408\u5f81\u6216\u6297\u836f\u7269\u6297\u4f53\u7684\u51fa\u73b0\uff09\u5c24\u4e3a\u91cd\u8981\u3002\u4f8b\u5982\uff0c\u53cc\u7279\u5f02\u6027T\u7ec6\u80de\u63a5\u5408\uff08BiTE\uff09\u6297\u4f53blinatumomab\uff08Blincyto\uff09\uff0c\u9488\u5bf9CD19\u548cCD3\uff0c\u5176\u534a\u8870\u671f\u7ea6\u4e3a2\u5c0f\u65f6\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u6700\u540e\uff0c\u65b0\u7684\u7ed9\u836f\u9014\u5f84\uff0c\u5982\u80bf\u7624\u5185\u7ed9\u836f\uff0c\u5e26\u6765\u4e86\u65b0\u7684\u6311\u6218\u3002\u8fd9\u8981\u6c42\u4e0d\u4ec5\u8bc4\u4f30\u836f\u7269\u5728\u5916\u5468\u8840\u4e2d\u7684\u836f\u4ee3\u52a8\u529b\u5b66\uff0c\u8fd8\u8981\u8bc4\u4f30\u5176\u5728\u5c40\u90e8\u7684\u6548\u679c\u3002\u56e0\u6b64\uff0c\u5bf9\u836f\u7269\u5236\u5242\u7684\u4f18\u5316\u53d8\u5f97\u8d8a\u6765\u8d8a\u91cd\u8981\uff0c\u4ee5\u786e\u4fdd\u836f\u7269\u5728\u6cbb\u7597\u533a\u57df\u7684\u6700\u5927\u53ef\u7528\u91cf\u548c\u7406\u60f3\u7684\u836f\u6548\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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32.2.3.2  \u836f\u6548\u5b66<\/p>\n<\/section>\n

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\u8bbe\u8ba1\u9002\u5f53\u7684\u836f\u6548\u5b66\u5206\u6790\u65b9\u6848\uff0c\u4ee5\u8bc4\u4f30\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u6ede\u5242\u7684\u7597\u6548\u5b58\u5728\u56f0\u96be\uff0c\u539f\u56e0\u5728\u4e8e\u5b83\u4eec\u8868\u8fbe\u6a21\u5f0f\u7684\u9ad8\u5ea6\u53d8\u5f02\u6027\u3002\u4f8b\u5982\uff0cPD-1\u4e3b\u8981\u8868\u8fbe\u5728T\u7ec6\u80de\u8868\u9762\uff0c\u800cCTLA-4\u901a\u5e38\u4ec5\u4e3a\u77ac\u65f6\u8868\u8fbe\uff0c\u4e14\u751f\u7269\u6807\u5fd7\u7269\u7684\u8868\u8fbe\u53ef\u80fd\u662f\u56fa\u6709\u7684\u6216\u662f\u88ab\u8bf1\u5bfc\u7684\u3002\u56e0\u6b64\uff0c\u5229\u7528\u6d41\u5f0f\u7ec6\u80de\u672f\u6765\u8bc4\u4f30\u5faa\u73afT\u7ec6\u80de\u4e0a\u7684\u53d7\u4f53\u5360\u7528\u60c5\u51b5\u662f\u53ef\u884c\u7684\uff0c\u4f46\u8fd9\u79cd\u65b9\u6cd5\u53ea\u9002\u7528\u4e8e\u5c11\u6570\u5206\u5b50\u3002\u8fd9\u79cd\u6280\u672f\u5df2\u7ecf\u6210\u529f\u5e94\u7528\u4e8enivolumab\u7684\u4e00\u671f\u8bd5\u9a8c\uff0c\u7814\u7a76\u53d1\u73b0\u53d7\u4f53\u5360\u7528\u7387\u4f3c\u4e4e\u4e0e\u5242\u91cf\u65e0\u5173\uff0c\u4e14\u6301\u7eed\u65f6\u95f4\u8f83\u957f\uff08\u6700\u540e\u4e00\u6b21\u7ed9\u836f\u540e3\u4e2a\u6708\u5185\u89c2\u5bdf\u5230\u5360\u7528\u7387\u4e0b\u964d\uff09\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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32.2.4   \u75c5\u4eba\u8d44\u683c<\/p>\n<\/section>\n

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\u7b2c\u4e09\uff0c\u6709\u65f6\u201c\u610f\u5916\u201d\u53cd\u5e94\u8005\u7684\u51fa\u73b0\u53ef\u4ee5\u4e3a\u6211\u4eec\u63d0\u4f9b\u6bd4\u7cbe\u5fc3\u6311\u9009\u7684\u540c\u8d28\u60a3\u8005\u961f\u5217\u66f4\u591a\u7684\u4fe1\u606f\uff0c\u5e2e\u52a9\u6211\u4eec\u66f4\u6df1\u5165\u5730\u4e86\u89e3\u836f\u7269\u7684\u4f5c\u7528\u673a\u5236\u548c\u6f5c\u5728\u7684\u76ee\u6807\u4eba\u7fa4\u3002\u8fd9\u79cd\u53d1\u73b0\u5f3a\u8c03\u4e86\u5728\u4e00\u671f\u8bd5\u9a8c\u4e2d\u4fdd\u6301\u5165\u9009\u6807\u51c6\u7684\u7075\u6d3b\u6027\u7684\u91cd\u8981\u6027\u3002<\/p>\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 | \u51bc\u91d1\u6b22<\/span><\/p>\n

\u56fe\u6587\u6392\u7248 | \u6f58\u541b\u541b<\/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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\u514d\u75ab\u5b66\u62fe\u9057\u7cfb\u5217<\/a><\/span><\/p>\n

\u80bf\u7624\u514d\u75ab\u5b66\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

RCIM\u4eea\u5668\u7b80\u4ecb\u53ca\u64cd\u4f5c\u89c6\u9891<\/a><\/span><\/p>\n

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

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

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