{"id":29301,"date":"2017-09-08T00:28:17","date_gmt":"2017-09-07T16:28:17","guid":{"rendered":"https:\/\/case.ntu.edu.tw\/blog\/?p=29301"},"modified":"2018-07-29T11:28:23","modified_gmt":"2018-07-29T03:28:23","slug":"%e7%99%8c%e7%97%87%e6%96%b0%e7%99%82%e6%b3%95%e7%9a%84%e5%b0%8b%e5%b0%8b%e8%a6%93%e8%a6%93-%e8%ae%93%e5%85%8d%e7%96%ab%e7%b3%bb%e7%b5%b1%e5%b9%ab%e4%bd%a0%e9%87%8f%e8%ba%ab%e8%a8%82%e4%bd%9c","status":"publish","type":"post","link":"https:\/\/case.ntu.edu.tw\/blog\/?p=29301","title":{"rendered":"\u764c\u75c7\u65b0\u7642\u6cd5\u7684\u5c0b\u5c0b\u8993\u8993\u2014\u8b93\u514d\u75ab\u7cfb\u7d71\u5e6b\u4f60\u91cf\u8eab\u8a02\u4f5c\uff01 \uff08\u4e0a\uff09"},"content":{"rendered":"

\u25a0\u5e38\u8e1e\u53f0\u7063\u5341\u5927\u6b7b\u56e0\u4e4b\u9996\u7684\u764c\u75c7\uff0c\u4e5f\u4e00\u76f4\u662f\u8b93\u5168\u7403\u5404\u5730\u91ab\u7642\u754c\u6293\u7834\u982d\u82e6\u60f3\u6cbb\u7642\u5c0d\u7b56\u7684\u982d\u865f\u9ebb\u7169\u75be\u75c5\u3002\u64da\u4e16\u754c\u885b\u751f\u7d44\u7e54 WHO \u4f30\u8a08\uff0c\u5168\u4e16\u754c\u7d04\u6bcf\u516d\u4ef6\u6b7b\u4ea1\u6848\u4f8b\uff0c\u5c31\u6709\u4e00\u4eba\u6b7b\u65bc\u764c\u75c7\u3002\u9664\u4e86\u624b\u8853\u79fb\u9664\uff0c\u820a\u6709\u6cbb\u7642\u7b56\u7565\u5e38\u8f14\u4ee5\u653e\u5c04\u7dda\u6cbb\u7642\u6216\u662f\u5316\u5b78\u85e5\u7269\u6cbb\u7642\uff1b\u4f46\u4e0d\u8ad6\u662f\u653e\u5c04\u7dda\u3001\u9084\u662f\u5316\u5b78\u7642\u6cd5\uff0c\u90fd\u96e3\u514d\u70ba\u4e86\u63ea\u51fa\u4e00\u500b\u764c\u75c7\u7d30\u80de\uff0c\u800c\u932f\u6bba\u4e00\u767e\u500b\u6b63\u5e38\u7d30\u80de\uff0c\u526f\u4f5c\u7528\u5982\u540c\u7389\u77f3\u4ff1\u711a\u822c\u6158\u70c8\u3002\u91ab\u7642\u7814\u7a76\u754c\u4e00\u76f4\u60f3\u8981\u627e\u5230\u4e00\u500b\u66f4\u70ba\u5c08\u4e00\u7684\u6cbb\u7642\u65b9\u6cd5\uff0c\u8b93\u60a3\u8005\u5728\u7642\u7a0b\u4e2d\uff0c\u9ad4\u5167\u6b63\u5e38\u5065\u5eb7\u7d30\u80de\u4e0d\u5c0f\u5fc3\u88ab\u9023\u5750\u800c\u8aa4\u6bba\u7684\u53ef\u80fd\u6027\u964d\u5230\u6700\u4f4e\u3002\u800c\u6700\u8b93\u5927\u5bb6\u61f7\u62b1\u5e0c\u671b\u7684\uff0c\u6b63\u662f\u9019\u5e7e\u5e74\u7576\u7d05\u7684\u764c\u75c7\u514d\u75ab\u6cbb\u7642\u3002<\/strong><\/span><\/p>\n

\"\"\u64b0\u6587\uff5c<\/strong>\u99f1\u5b9b\u7433<\/p>\n

\u300c\u764c\u75c7\u514d\u75ab\u6cbb\u7642\u300d\uff0c\u7b56\u7565\u5982\u5176\u540d\uff0c\u5c31\u662f\u7528\u60a3\u8005\u9ad4\u5167\u7684\u514d\u75ab\u5927\u8ecd\u4f86\u8a0e\u4f10\u764c\u75c7\u7d30\u80de\u3002\u514d\u75ab\u7cfb\u7d71\u8fa8\u5225\u6575\u6211\u7684\u5c08\u4e00\u6027\u3001\u654f\u92b3\u6027\u5728\u9577\u6642\u9593\u7684\u6f14\u5316\u88e1\uff0c\u65e9\u5df2\u7df4\u5f97\u4e00\u8eab\u7368\u9580\u770b\u5bb6\u672c\u9818\u3002\u514d\u75ab\u7cfb\u7d71\u9664\u4e86\u4fdd\u8b77\u500b\u9ad4\u4e0d\u53d7\u5916\u4f86\u75c5\u539f\u83cc\u5165\u4fb5\uff0c\u4e5f\u76ef\u68a2\u8457\u9ad4\u5167\u7d30\u80de\u6709\u6c92\u6709\u51fa\u73fe\u4e0d\u6b63\u5e38\u8b8a\u7570\u3002\u5982\u679c\u6709\u5075\u6e2c\u5230\u7591\u4f3c\u75c5\u8b8a\u7684\u7d30\u80de\uff0c\u4e5f\u6703\u89f8\u52d5\u8b66\u9234\u800c\u6d3b\u5316\u514d\u75ab\u7d30\u80de\u5c07\u75c5\u8b8a\u7d30\u80de\u6d88\u6ec5\u3002<\/p>\n

\u4f46\u764c\u75c7\u816b\u7624\u5167\u6216\u5468\u908a\u9644\u8fd1\u7684\u74b0\u5883\uff0c\u5f80\u5f80\u50cf\u662f\u6492\u4e86\u7279\u5225\u91dd\u5c0d\u514d\u75ab\u7d30\u80de\u7684\u8ff7\u9b42\u5e33\u4e00\u6a23\uff1b\u514d\u75ab\u7d30\u80de\u5728\u816b\u7624\u5167\uff0c\u65e2\u53cd\u61c9\u9072\u920d\u4e5f\u529f\u80fd\u505c\u64fa\u3002\u56e0\u6b64\uff0c\u5982\u4f55\u8b93\u514d\u75ab\u7cfb\u7d71\u5728\u816b\u7624\u5468\u908a\u74b0\u5883\u80fd\u5920\u300c\u56de\u795e\u300d\u800c\u6062\u5fa9\u5e73\u5e38\u6c34\u6e96\uff0c\u6b63\u662f\u764c\u75c7\u514d\u75ab\u6cbb\u7642\u7684\u76ee\u6a19\u3002<\/p>\n

\u65e9\u5728\u5341\u4e5d\u4e16\u7d00\u672b\u3001\u4e8c\u5341\u4e16\u7d00\u521d\u671f\uff0c\u81e8\u5e8a\u4e0a\u5c31\u6709\u5229\u7528\u523a\u6fc0\u514d\u75ab\u7cfb\u7d71\u4f86\u62b5\u6297\u764c\u75c7\u7684\u7d00\u9304\u3002\u90a3\u6642\u5019Coley\u91ab\u751f\u5c07\u5e7e\u7a2e\u7d30\u83cc\u6df7\u5728\u4e00\u8d77\u518d\u7528\u9ad8\u6eab\u6bba\u6b7b\uff0c\u6ce8\u5c04\u5230\u764c\u75c7\u75c5\u4eba\u9ad4\u5167\uff0c\u5e0c\u671b\u85c9\u7531\u6b7b\u7d30\u83cc\u682a\u4f86\u6d3b\u5316\u75c5\u4eba\u5167\u7684\u514d\u75ab\u53cd\u61c9\u3002\u5f8c\u4f86\uff0c\u96a8\u8457\u624b\u8853\u8207\u653e\u5c04\u7dda\u3001\u5316\u5b78\u7642\u6cd5\u7684\u666e\u53ca\uff0cColey\u7684\u7368\u9580\u914d\u65b9\u4e5f\u5c31\u8d70\u5165\u6b77\u53f2\u3002\u800c\u96a8\u8457\u514d\u75ab\u5b78\u7684\u84ec\u52c3\u767c\u5c55\uff0c\u73fe\u4eca\u7684\u764c\u75c7\u514d\u75ab\u6cbb\u7642\u5247\u6709\u7b56\u7565\u591a\u4e86\u3002<\/p>\n

\u76ee\u524d\uff0c\u764c\u75c7\u514d\u75ab\u6cbb\u7642\u7684\u9996\u63a8\u4ee5\u300cCTLA-4\u300d\u8207\u300cPD-1\u300d\u70ba\u9776\u9ede\u7684\u7b56\u7565\u3002CTLA-4 \u548c PD-1 \u90fd\u662f\u8868\u73fe\u5728T\u7d30\u80de\u4e0a\u7684\u514d\u75ab\u6291\u5236\u578b\u53d7\u9ad4\uff0c\u662fT\u7d30\u80de\u53cd\u61c9\u7684\u524e\u8eca\u677f\u3002\u7576 CTLA-4 \u548c PD-1 \u7d50\u5408\u5230\u5404\u81ea\u5c0d\u61c9\u7684\u914d\u9ad4\u800c\u88ab\u523a\u6fc0\u6d3b\u5316\u7684\u6642\u5019\uff0c\u5c31\u6703\u555f\u52d5T\u7d30\u80de\u5167\u7684\u514d\u75ab\u6291\u5236\u8a0a\u606f\u50b3\u5c0e\u8ff4\u8def\uff0c\u8b93T\u7d30\u80de\u6240\u8ca0\u8cac\u7684\u4e0b\u6e38\u514d\u75ab\u53cd\u61c9\u90fd\u4eae\u7d05\u71c8\u7121\u6cd5\u88ab\u6709\u6548\u57f7\u884c\u3002\u5728\u5065\u5eb7\u60c5\u6cc1\u4e0b\uff0c\u88ab\u826f\u597d\u8abf\u63a7\u7684 PD-1 \u8207 CTLA-4 \u514d\u75ab\u6291\u5236\u8ff4\u8def\u53ef\u4ee5\u4fdd\u8b77\u6b63\u5e38\u81ea\u9ad4\u7d44\u7e54\u4e0d\u88ab\u8aa4\u8a8d\u70ba\u5916\u4fae\uff0c\u9632\u6b62\u514d\u75ab\u7cfb\u7d71\u653b\u64ca\u81ea\u8eab\u7d44\u7e54\u800c\u5f15\u8d77\u81ea\u9ad4\u514d\u75ab\u75be\u75c5\u3002<\/p>\n

\u800c\u5728\u816b\u7624\u5167\uff0c\u8a31\u591a\u764c\u75c7\u7d30\u80de\u90fd\u85c9\u8457\u8868\u73fe\u5927\u91cf PD-1 \u7684\u914d\u9ad4 PD-L1\uff0c\u4f86\u85c9\u7531\u6d3b\u5316 PD-1 \u8a0a\u606f\u50b3\u5c0e\uff0c\u597d\u6291\u5236T\u7d30\u80de\u6d3b\u6027\u3002\u800c\u4ee5T\u7d30\u80de\u6240\u8868\u73fe\u7684 CTLA-4\u3001PD-1 \u6216\u662f\u764c\u75c7\u7d30\u80de\u8868\u73fe\u914d\u9ad4 PD-L1 \u70ba\u9776\u9ede\u7684\u6cbb\u7642\uff0c\u5c31\u662f\u5e0c\u671b\u85c9\u7531\u7d66\u4e88\u60a3\u8005\u80fd\u5920\u963b\u65b7 PD-1 \u6216 CTLA-4 \u529f\u80fd\u7684\u6297\u9ad4\uff0c\u8b93\u514d\u75ab\u7cfb\u7d71\u524e\u8eca\u677f\u5728\u53ef\u4ee5\u5bb9\u8a31\u7684\u7bc4\u570d\u5167\u7a0d\u5fae\u5931\u9748\uff0c\u9032\u800c\u63d0\u9ad8T\u7d30\u80de\u7684\u6d3b\u6027\u3002\u76ee\u524d\uff0c\u91dd\u5c0d CTLA-4 \u7684\u6297\u9ad4\u6709 Tremelimumab \u548c Ipillmumab\uff0c\u963b\u65b7 PD-1 \u7684\u6297\u9ad4\u5247\u6709 Pembrolizumab \u8207 Nivolumab\uff0c\u800c\u8b93\u764c\u75c7\u7d30\u80de\u5927\u91cf\u8868\u73fe\u7684 PD-L1 \u7121\u6cd5\u8a6d\u8a08\u5f97\u901e\u7684\u5247\u6709 Durvalumab \u8207 Avelumab\uff0c\u8ddf\u9019\u5e7e\u500b\u9776\u9ede\u6cbb\u7642\u76f8\u95dc\u7684\u81e8\u5e8a\u8a66\u9a57\u4e5f\u662f\u591a\u5982\u904e\u6c5f\u4e4b\u9bfd\uff0c\u81e8\u5e8a\u4e0a\u7684\u597d\u6d88\u606f\u66f4\u662f\u63a5\u4e8c\u9023\u4e09\u3002\u5c24\u5176\u662f\u300cPD-1\u300d\u76f8\u95dc\u7684\u6cbb\u7642\u7b56\u7565\uff0c\u300c\u7206\u7d05\u300d\u53ef\u80fd\u90fd\u4e0d\u8db3\u4ee5\u5f62\u5bb9\u5176\u5728\u81e8\u5e8a\u8207\u79d1\u5b78\u7814\u7a76\u53d7\u5bf5\u7684\u7a0b\u5ea6\uff1a\u5f9e\u9ed1\u8272\u7d20\u7624\u76ae\u819a\u764c\u3001\u80ba\u764c\u3001\u8180\u80f1\u764c\u3001\u80c3\u764c\u3001\u814e\u7d30\u80de\u764c\u3001\u982d\u9838\u90e8\u764c\uff0c\u5230\u6dcb\u5df4\u764c\uff0c\u300cPD-1\u300d\u70ba\u672c\u7684\u6a19\u9776\u6cbb\u7642\u4f3c\u4e4e\u662f\u6230\u7121\u4e0d\u52dd \u3002<\/p>\n

\u4f46\u524e\u8eca\u677f\u4e0d\u9748\u654f\u7684 T \u7d30\u80de\u4e5f\u6709\u5176\u6f5b\u5728\u96b1\u6182\u3002\u514d\u75ab\u7cfb\u7d71\u4e4b\u6240\u4ee5\u5167\u5efa\u4e86\u8a31\u591a\u6291\u5236\u514d\u75ab\u53cd\u61c9\u7684\u8ff4\u8def\uff0c\u5c31\u662f\u5e0c\u671b\u514d\u75ab\u7cfb\u7d71\u5728\u88ab\u6d3b\u5316\u524d\uff0c\u6709\u91cd\u91cd\u95dc\u5361\u53ef\u4ee5\u78ba\u8a8d\u5176\u6b32\u5bb0\u6bba\u5c0d\u8c61\u662f\u6575\u975e\u6211\u3002\u85c9\u7531\u6297\u9ad4\u7d66\u85e5\uff0c\u96d6\u963b\u65b7\u4e86\u6291\u5236\u7cfb\u7d71\u7684\u8a0a\u865f\u50b3\u905e\uff0c\u8b93\u514d\u75ab\u7d30\u80de\u4e0d\u88ab\u7d81\u624b\u7d81\u8173\uff0c\u537b\u4e5f\u50cf\u5728\u81ea\u5bb6\u5f8c\u9662\u7684\u7f8a\u5708\u88e1\u990a\u4e86\u982d\u72fc\uff0c\u5c0d\u60a3\u8005\u672c\u8eab\u7684\u5065\u5eb7\u7d30\u80de\u6709\u4e00\u5b9a\u7a0b\u5ea6\u7684\u5a01\u8105\u3002\u5f15\u8d77\u81ea\u9ad4\u514d\u75ab\u75be\u75c5\u526f\u4f5c\u7528\u7684\u96b1\u6182\uff0c\u4e5f\u4e00\u76f4\u662f\u764c\u75c7\u514d\u75ab\u6cbb\u7642\u7b56\u7565\u7684\u6700\u5927\u7f69\u9580\u3002<\/p>\n

\u800c\u7684\u78ba\uff0c\u81ea\u9ad4\u514d\u75ab\u75be\u75c5\u662f\u764c\u75c7\u514d\u75ab\u7642\u6cd5\u6700\u8b93\u4eba\u8292\u80cc\u5728\u523a\u7684\u526f\u4f5c\u7528\u3002\u4f8b\u5982\uff0c\u963b\u65b7 CTLA-4 \u529f\u80fd\u7684\u6297\u9ad4 ipilimumab\uff0c\u5728\u5404\u81e8\u5e8a\u7814\u7a76\u4e2d\uff0c\u6709 1% \u5230 25% \u4e0d\u7b49\u7684\u75c5\u4eba\uff0c\u6703\u51fa\u73fe\u8166\u4e0b\u5782\u9ad4\u708e\uff08hypophysitis\uff09\u7684\u81ea\u9ad4\u514d\u75ab\u75be\u75c5\u3002\u76ee\u524d\u7814\u7a76\u61f7\u7591\uff0c\u53ef\u80fd\u662f\u56e0\u70ba\u8166\u4e0b\u5782\u9ad4\u5167\u8ca0\u8cac\u5206\u6ccc\u723e\u8499\u7684\u7d30\u80de\u4e5f\u6703\u8868\u73fe CTLA-4\uff0c\u56e0\u6b64\u7576\u963b\u65b7 CTLA-4 \u7684\u6297\u9ad4\u6295\u4e88\u75c5\u4eba\u5f8c\uff0cCTLA-4 \u6297\u9ad4\u9664\u4e86\u7d50\u5408\u4e0aT\u7d30\u80de\uff0c\u4e5f\u7d50\u5408\u4e0a\u4e86\u8166\u4e0b\u5782\u9ad4\u7d30\u80de\u4e0a\u7684 CTLA-4\uff0c\u6d3b\u5316\u5148\u5929\u514d\u75ab\u7684\u88dc\u9ad4\u7cfb\u7d71\uff0c\u800c\u5f15\u8d77\u767c\u708e\u53cd\u61c9\u3002<\/p>\n

\u9019\u8b93\u60f3\u8981\u7814\u767c\u764c\u75c7\u514d\u75ab\u6cbb\u7642\u7684\u81e8\u5e8a\u79d1\u5b78\u7814\u7a76\uff0c\u60f3\u8981\u53e6\u8b00\u5176\u4ed6\u53ef\u884c\u7684\u7b56\u7565\uff0c\u671f\u671b\u53ef\u4ee5\u975e\u5e38\u5c08\u4e00\u5730\uff0c\u53ea\u6d3b\u5316\u90a3\u4e9b\u80fd\u5920\u7784\u6e96\u764c\u75c7\u7d30\u80de\u767c\u52d5\u653b\u64ca\u7684T\u7d30\u80de\uff0c\u800c\u8b93\u5176\u4ed6\u8fa8\u8a8d\u4e0d\u4e86\u764c\u75c7\u7d30\u80de\u7684\u514d\u75ab\u7d30\u80de\u4ecd\u7136\u80fd\u5920\u6709\u5f37\u800c\u6709\u529b\u7684\u524e\u8eca\u677f\uff0c\u964d\u4f4e\u81ea\u9ad4\u514d\u75ab\u75be\u75c5\u526f\u4f5c\u7528\u7684\u53ef\u80fd\u6027\u3002\u800c\u9019\u500b\u6cbb\u7642\u7b56\u7565\uff0c\u53ef\u884c\u55ce\uff1f\u6311\u6230\u53c8\u5728\u54ea\u88e1\u5462\uff1f<\/p>\n

 <\/p>\n

\u53c3\u8003\u8cc7\u6599\uff1a<\/strong><\/p>\n

    \n
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  2. Naidoo J et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2016 Jul;27(7):1362. doi: 10.1093\/annonc\/mdw141. Epub 2016 Apr 12. PMID: 27072927<\/li>\n
  3. Iwama S et al. Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody. Sci Transl Med. 2014 Apr 2;6(230):230ra45. doi: 10.1126\/scitranslmed.3008002. PMID: 24695685<\/li>\n
  4. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017 Jan 18;541(7637):321-330. doi: 10.1038\/nature21349.<\/li>\n<\/ol>\n

    --<\/strong><\/span>
    \n\u4f5c\u8005\uff1a\u99f1\u5b9b\u7433\u3000\u7f8e\u570b\u8056\u8def\u6613\u83ef\u76db\u9813\u5927\u5b78\uff08Washington University in St. Louis\uff09\u514d\u75ab\u5b78\u535a\u58eb\uff0c\u5f9e\u4e8bT\u7d30\u80de\u767c\u80b2\u8207\u6d3b\u5316\u76f8\u95dc\u7684\u8a0a\u606f\u50b3\u5c0e\u7814\u7a76\u3002<\/strong><\/span><\/p>\n

     <\/p>\n

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