{"id":28204,"date":"2022-07-28T00:21:21","date_gmt":"2022-07-27T16:21:21","guid":{"rendered":"https:\/newsletter.sinica.edu.tw\/?p=28204"},"modified":"2023-03-09T10:17:29","modified_gmt":"2023-03-09T02:17:29","slug":"%e3%80%90%e5%b0%88%e6%ac%84%e3%80%91the-good%e5%85%8d%e7%96%ab%e7%b4%b0%e8%83%9e-the-bad%e7%99%8c%e7%b4%b0%e8%83%9e-and-the-ugly%e7%b4%b0%e8%8f%8c-%e6%b7%ba%e8%ab%87%e7%b4%b0","status":"publish","type":"post","link":"https:\/newsletter.sinica.edu.tw\/28204\/","title":{"rendered":"\u3010\u5c08\u6b04\u3011The Good(\u514d\u75ab\u7d30\u80de), the Bad(\u764c\u7d30\u80de), and the Ugly(\u7d30\u83cc) \u2014 \u6dfa\u8ac7\u7d30\u83cc\u764c\u75c7\u7642\u6cd5"},"content":{"rendered":"

\u201cThe Good, the Bad, and the Ugly\u201d (\u4e2d\u6587\u8b6f\u4f5c\u300a\u9ec3\u660f\u4e09\u93e2\u5ba2\u300b) \u662f\u7fa9\u5927\u5229\u5c0e\u6f14\u8cfd\u5409\u6b50\uff0e\u674e\u6602\uff08Sergio Leone\uff09\u65bc 1966 \u5e74\u63a8\u51fa\u7684\u7d93\u5178\u897f\u90e8\u96fb\u5f71\uff0c\u5287\u4e2d\u63cf\u8ff0\u4e09\u500b\u6027\u683c\u8fe5\u7570\u7684\u4e3b\u89d2\u5728\u8ffd\u9010\u5bf6\u85cf\u7684\u904e\u7a0b\u6240\u767c\u751f\u7684\u885d\u7a81\u8207\u8da3\u4e8b\u3002\u7b46\u8005\u5728\u69cb\u601d\u6b64\u6587\u6642\uff0c\u7a81\u7136\u60f3\u5230\u9019\u90e8\u96fb\u5f71\u53ef\u4ee5\u7528\u4f86\u6bd4\u64ec\u7d30\u83cc\u764c\u75c7\u7642\u6cd5\uff08Bacteria-based cancer therapy\uff09\u4e2d\u7684\u4e09\u500b\u8981\u89d2\uff1a\u300c\u514d\u75ab\u7d30\u80de (the Good)\u300d\u3001\u300c\u764c\u7d30\u80de (the Bad)\u300d\u3001\u8207\u300c\u7d30\u83cc (the Ugly)\u300d\u3002\u9019\u4e09\u500b\u89d2\u8272\u90fd\u662f\u6d3b\u7684\u7d30\u80de\uff0c\u7af6\u722d\u8457\u76f8\u540c\u7684\u8cc7\u6e90\uff0c\u96a8\u6642\u4fdd\u6301\u8457\u52d5\u614b\u7684\u4e92\u52d5\u95dc\u4fc2\u3002\u5c31\u50cf\u5728\u96fb\u5f71\u4e2d\uff0cthe Good \u60f3\u8981\u6253\u8d0f the Bad\uff0c\u5f80\u5f80\u9084\u5f97\u9760\u8457\u8ddfthe Ugly \u7684\u5408\u4f5c\u3002\u8981\u5982\u4f55\u5229\u7528\u7d30\u83cc\u4f86\u5e6b\u52a9\u514d\u75ab\u7cfb\u7d71\u6253\u8d0f\u764c\u75c7\uff0c\u9019\u5c31\u662f\u7d30\u83cc\u764c\u75c7\u7642\u6cd5\u7684\u7814\u7a76\u6838\u5fc3\u3002\u4ee5\u4e0b\u7b46\u8005\u8a66\u5716\u6dfa\u8ac7\u9019\u500b\u65b0\u8208\u7684\u9818\u57df 1-3<\/sup>\u3002<\/p>\n

\u7b2c\u4e00\u500b\u6d3b\u7684\u85e5\u7269\uff1aCAR-T \u7642\u6cd5<\/strong><\/p>\n

\u8b1b\u5230\u6d3b\u7684\u85e5\u7269 (live drugs)\uff0c\u76f8\u4fe1\u5927\u5bb6\u5c0d CAR-T(Chimeric antigen receptor T-cell therapy\uff0c\u4e2d\u6587\u8b6f\u4f5c\u5d4c\u5408\u6297\u539f\u53d7\u9ad4 T \u7d30\u80de\u7642\u6cd5)\u4e26\u4e0d\u964c\u751f\u3002\u5728 2010-2011 \u5e74\uff0c\u7f8e\u570b\u7684\u4e09\u500b\u5718\u968a(Steven Rosenberg, Carl June, and Michel Sadelain)\u5206\u5225\u767c\u8868\u4e86\u4e09\u7bc7\u81e8\u5e8a\u8ad6\u6587\uff0c\u8b49\u660e anti-CD19 CAR-T therapy \u5c0d\u65bc B \u7d30\u80de\u8840\u764c\u6709\u6975\u4f73\u7684\u7642\u6548 1-3\u3002 \u4f8b\u5982\uff0c\u5c0f\u5973\u5b69\u827e\u871c\u8389 (Emily Whitehead) \u662f\u4eba\u985e\u6b77\u53f2\u4e0a\u7b2c\u4e00\u4f4d\u63a5\u53d7 CAR-T \u6cbb\u7642\u7684\u5b69\u7ae5\u3002\u5979\u5728 6 \u6b72\u6642\u7f79\u60a3\u4e86\u8840\u764c\u672b\u671f\uff0c\u7d93\u6b77\u5404\u7a2e\u6cbb\u7642\u90fd\u5931\u6557\u5f8c\uff0c\u5979\u5617\u8a66\u4e86 CAR-T \u7684\u81e8\u5e8a\u8a66\u9a57\uff0c\u6210\u529f\u300c\u6cbb\u7652\u300d\u4e86\u5979\u7684\u764c\u75c7\uff0c\u5982\u4eca\u5df2\u7d93\u5341\u5e74\u6c92\u6709\u5fa9\u767c\uff0c\u7db2\u8def\u4e0a\u53ef\u4ee5\u770b\u5230\u5979\u6bcf\u5e74\u6176\u795d cancer-free \u7684\u53ef\u611b\u7167\u7247\u3002\u50cf\u827e\u871c\u8389\u9019\u6a23\u6210\u529f\u7684\u4f8b\u5b50\u4e26\u4e0d\u7f55\u898b\uff0c\u6839\u64da\u6700\u8fd1\u7684\u7d71\u8a08\uff0cCAR-T \u7642\u6cd5\u5c0d\u65bc\u9069\u61c9\u75c7\u7684\u6210\u529f\u7387\u9054\u5230\u4e86 50-80%\uff0c\u5176\u4e2d\u591a\u6578\u75c5\u4eba (30-40%) \u90fd\u53ef\u4ee5\u5f97\u5230\u9577\u671f\u7684\u7121\u764c\u751f\u5b58\u3002\u57fa\u65bc\u5982\u6b64\u512a\u7570\u7684\u85e5\u6548\uff0c\u7f8e\u570b\u98df\u85e5\u7f72\u5728 2017 \u5e74\u6b63\u5f0f\u6838\u51c6\u4e86\u5169\u652f CAR-T \u85e5\u7269 (Kymriah and Yescarta)\uff0c\u9069\u7528\u65bc\u591a\u7a2e B \u7d30\u80de\u8840\u764c\u6cbb\u7642\u3002<\/p>\n

CAR-T \u7642\u6cd5\u662f\u5c07\u75c5\u4eba\u8840\u6db2\u4e2d\u7684 T \u7d30\u80de\u53d6\u51fa\uff0c\u5728\u5be6\u9a57\u5ba4\u88e1\u900f\u904e\u57fa\u56e0\u5de5\u7a0b\u7684\u65b9\u5f0f\u6539\u9020\uff0c\u4f7f\u5176\u80fd\u8fa8\u8b58\u7279\u5b9a\u764c\u75c7\u6297\u539f (\u4f8b\u5982 B \u7d30\u80de\u8840\u764c\u7684CD19)\uff0c\u518d\u5c07\u6539\u9020\u5f8c\u7684 T \u7d30\u80de\u6ce8\u56de\u75c5\u4eba\u9ad4\u4e2d\uff0c\u884c\u4f7f\u653b\u64ca\u764c\u7d30\u80de\u7684\u4efb\u52d9\u3002\u7531\u65bc CAR-T \u662f\u6d3b\u7684\u7d30\u80de\uff0c\u9032\u5165\u4eba\u9ad4\u5f8c\uff0c\u5728\u764c\u75c7\u6297\u539f\u7684\u523a\u6fc0\u4e0b\uff0c\u6703\u4e0d\u65b7\u518d\u751f\uff0c\u7522\u751f\u66f4\u591a CAR-T \u7d30\u80de\u4f86\u653b\u64ca\u764c\u7d30\u80de\u3002\u6bd4\u8d77\u50b3\u7d71\u7684\u85e5\u7269\u6cbb\u7642\uff0c\u9700\u8981\u9577\u671f\u591a\u6b21\u7684\u6295\u85e5\uff0c CAR-T \u539f\u5247\u4e0a\u50c5\u9700\u8981\u4e00\u6b21\u6027\u7684\u6cbb\u7642 (\u57fa\u65bc\u5b89\u5168\u8003\u91cf\uff0c \u5be6\u969b\u81e8\u5e8a\u64cd\u4f5c\u901a\u5e38\u662f\u4e00\u5468\u5167\u9032\u884c 2-3 \u6b21 CAR-T \u6ce8\u5c04\uff0c\u5f9e\u4f4e\u5291\u91cf\u5230\u9ad8\u5291\u91cf\uff0c\u907f\u514d\u5f37\u70c8\u7684\u526f\u4f5c\u7528\u7522\u751f)\uff0c\u5c31\u53ef\u4ee5\u9054\u5230\u7d42\u8eab\u7684\u7642\u6548\u3002\u503c\u5f97\u4e00\u63d0\u7684\u662f\uff0c\u5982\u679c\u9078\u64c7\u4f7f\u7528\u4ee5 4-1BB \u4f5c\u70ba co-stimulation domain \u7684Kymriah\uff0c CAR-T \u7d30\u80de\u9664\u4e86\u5728\u6295\u85e5\u4e00\u500b\u6708\u5167\u6703\u5927\u91cf\u589e\u751f\u4ee5\u5916\uff0c\u96a8\u5f8c CAR-T \u6703\u5206\u5316\u6210 memory T \u7d30\u80de\uff0c\u5c11\u91cf\u4e26\u9577\u671f\u5730\u5b58\u5728\u4eba\u9ad4\u5167\uff0c\u6700\u9ad8\u7d00\u9304\u5728\u6cbb\u7642\u8d85\u904e\u5341\u5e74\u7684\u75c5\u4eba\u9ad4\u5167\u4ecd\u80fd\u5075\u6e2c\u5230 CAR-T \u7684\u5b58\u5728\uff0c\u9019\u53ef\u80fd\u89e3\u91cb\u4e86\u70ba\u4f55 CAR-T \u80fd\u9577\u671f\u9632\u6b62\u764c\u75c7\u5fa9\u767c\u7684\u6a5f\u5236 4<\/sup>\u3002<\/p>\n

\u4ec0\u9ebc\uff1f\u7d30\u83cc\u80fd\u6cbb\u764c\u75c7\uff1f<\/strong><\/p>\n

\u5982\u679c\u8981\u7c21\u8ff0\u4e00\u4e0b\u4eba\u985e\u5c0d\u6297\u764c\u75c7\u7684\u6b77\u53f2 (\u5716\u4e00 )\uff0c\u4eba\u985e\u5f9e\u516c\u5143\u524d 3000 \u5e74\u5c31\u6709\u8a18\u8f09\u4f7f\u7528\u5207\u9664\u7684\u65b9\u5f0f\u4f86\u6cbb\u7642\u764c\u75c7\u3002\u4e00\u76f4\u5230\u4e86 20 \u4e16\u7d00\u521d\u671f\uff0c\u7531\u65bc\u5c45\u91cc\u5148\u751f\u8207\u592b\u4eba\u767c\u73fe\u4e86 X-ray\uff0c\u653e\u5c04\u6cbb\u7642\u624d\u6210\u70ba\u4e86\u5916\u79d1\u624b\u8853\u4ee5\u5916\u7b2c\u4e8c\u500b\u91ab\u754c\u8a8d\u53ef\u7684\u764c\u75c7\u7642\u6cd5\u3002\u5230\u4e86 20 \u4e16\u7d00\u4e2d\u8449\uff0c\u5316\u7642\u85e5\u7269\u958b\u59cb\u8208\u76db\uff0c\u6210\u70ba\u764c\u75c7\u6cbb\u7642\u7684\u4e3b\u6d41\uff0c\u4f46\u5176\u5f37\u70c8\u7684\u526f\u4f5c\u7528\u5f80\u5f80\u4ee4\u75c5\u4eba\u671b\u4e4b\u537b\u6b65\u3002 1980 \u5e74\u4ee3\u958b\u59cb\uff0c\u79d1\u5b78\u5bb6\u767c\u5c55\u51fa\u6a19\u9776\u6cbb\u7642\uff0c\u5176\u4e2d\u5305\u62ec\u5c0f\u5206\u5b50\u85e5\u7269\u7684 tyrosine kinase inhibitors \u4ee5\u53ca\u5927\u5206\u5b50\u85e5\u7269\u7684\u6297\u9ad4\u3002\u6a19\u9776\u85e5\u7269\u7684\u51fa\u73fe\uff0c\u5927\u5927\u964d\u4f4e\u4e86\u764c\u75c7\u6cbb\u7642\u7684\u526f\u4f5c\u7528\uff0c\u662f\u764c\u75c7\u75c5\u60a3\u7684\u4e00\u5927\u798f\u97f3\u3002\u7136\u800c\u4e0d\u8ad6\u662f\u653e\u5c04\u6cbb\u7642\u3001\u5316\u5b78\u6cbb\u7642\u3001\u9084\u662f\u6a19\u9776\u6cbb\u7642\uff0c\u5f80\u5f80\u90fd\u53ea\u80fd\u5ef6\u7de9\u764c\u75c7\u7684\u9032\u7a0b\uff0c\u7121\u6cd5\u771f\u6b63\u300c\u6cbb\u7652\u300d\u764c\u75c7\u3002\u76f4\u5230 2010 \u5e74\u4ee3\uff0c\u7531\u65bc\u514d\u75ab\u6aa2\u67e5\u9ede (immune checkpoint) \u7684\u767c\u73fe\uff0c\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\u5728\u591a\u7a2e\u764c\u75c7\u75c5\u4eba\u8eab\u4e0a\u5c55\u73fe\u5353\u8d8a\u7684\u7642\u6548\uff0c\u7d04\u83ab\u6709 20% \u7684\u75c5\u4eba\u80fd\u9054\u5230\u9577\u671f\u7de9\u89e3\u7684\u6548\u679c\u3002\u518d\u52a0\u4e0a 2017 \u5e74\u7372\u51c6\u7684 CAR-T \u80fd\u6709\u6548\u6cbb\u7652\u8840\u764c\uff0c\u4eba\u985e\u7d42\u65bc\u767c\u73fe\u5c0d\u6297\u764c\u75c7\u6700\u4f73\u7684\u6b66\u5668\u5c31\u662f\u81ea\u8eab\u7684\u514d\u75ab\u7cfb\u7d71\uff0c\u300c\u514d\u75ab\u7642\u6cd5\u300d(immunotherapy) \u7684\u7d00\u5143\u6b63\u5f0f\u958b\u59cb\u3002<\/p>\n

\"\u3010\u5c08\u6b04\u3011The

\u25b2\u5716\u4e00 \u764c\u75c7\u7642\u6cd5\u7c21\u53f2\u3002 1891 \u5e74\u70ba\u67ef\u7acb\u91ab\u751f\u7b2c\u4e00\u6b21\u5617\u8a66\u7d30\u83cc\u7642\u6cd5\u3002\u4e2d\u9593\u6b77\u7d93\u653e\u5c04\u6cbb\u7642\u3001\u5316\u5b78\u7642\u6cd5\u3001\u6a19\u9776\u6cbb\u7642\u3001\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\u3001\u7d30\u80de\u7642\u6cd5\uff0c\u5982\u4eca\u7d30\u83cc\u7642\u6cd5\u518d\u6b21\u9032\u5165\u81e8\u5e8a\u5be6\u9a57\uff0c\u6709\u671b\u63a5\u68d2\u7d30\u80de\u7642\u6cd5\u6210\u70ba\u4e0b\u500b\u4e16\u4ee3\u7684\u514d\u75ab\u7642\u6cd5\u3002<\/p><\/div>\n

\u4ee5\u4e0a\u662f\u4eba\u985e\u300c\u4e3b\u6d41\u300d\u7684\u6297\u764c\u53f2\uff0c\u7136\u800c\u6b77\u53f2\u4e0a\u66fe\u7d93\u6709\u4e00\u500b\u9577\u671f\u88ab\u5ffd\u8996\u7684\u7642\u6cd5 –\u300c\u7d30\u83cc\u764c\u75c7\u7642\u6cd5\u300d\uff0c\u662f\u7531\u7f8e\u570b\u91ab\u751f\u67ef\u7acb (William Coley) \u6240\u7814\u767c\u7684\u4e00\u7a2e\u5be6\u9a57\u6027\u7642\u6cd5\u3002\u6709\u95dc\u67ef\u7acb\u7684\u6545\u4e8b\uff0c\u672c\u9662\u9676\u79d8\u83ef\u7814\u7a76\u54e1\u8207\u5433\u5609\u4ec1\u535a\u58eb\u5728 1622 \u671f\u7684\u9662\u8a0a\u4e2d\u6709\u7cbe\u5f69\u7684\u6558\u8ff0\uff0c\u9019\u908a\u50c5\u6458\u8981\u5e7e\u500b\u91cd\u9ede\uff1a\u67ef\u7acb\u91ab\u751f\u5728 1891 \u5e74\uff0c\u9996\u6b21\u5617\u8a66\u5c07\u5316\u81bf\u6027\u93c8\u7403\u83cc (Streptococcus pyogenes\uff0c\u5927\u5bb6\u5e38\u7528\u7684 CRISPR\/Cas9 \u5373\u662f\u4f86\u81ea\u6b64\u83cc) \u6253\u5165\u75c5\u4eba\u816b\u7624\u5167\uff0c\u5c07\u4e00\u500b\u63a5\u8fd1\u62f3\u982d\u5927\u5c0f\u7684\u9838\u90e8\u8089\u7624\u764c\u5b8c\u5168\u6d88\u9664\u3002\u5176\u5f8c\u7684 30 \u5e74\u9593\uff0c\u67ef\u7acb\u91ab\u751f\u81f4\u529b\u65bc\u4f7f\u7528\u7d30\u83cc\u7642\u6cd5\u6cbb\u7642\u8d85\u904e 1000 \u4f4d\u75c5\u4eba\uff0c\u5176\u4e2d\u6709 500 \u4f4d\u4ee5\u4e0a\u5728\u6cbb\u7642\u671f\u9593\u9054\u5230\u63a5\u8fd1\u5b8c\u5168\u7de9\u89e3 (\u7f3a\u4e4f\u5f8c\u7e8c\u7684\u8ffd\u8e64\u7d00\u9304)\u3002<\/p>\n

\u7136\u800c\u67ef\u7acb\u91ab\u751f\u7576\u6642\u4e26\u4e0d\u80fd\u89e3\u91cb\u7d30\u83cc\u7642\u6cd5\u7684\u6a5f\u5236 (\u4e8b\u5be6\u4e0a\uff0c\u67ef\u7acb\u91ab\u751f\u9023\u764c\u75c7\u751f\u6210\u7684\u6a5f\u5236\u4e5f\u4e0d\u4e86\u89e3\uff0c\u4ed6\u4e00\u76f4\u5728\u53bb\u4e16\u524d\u90fd\u4ee5\u70ba\u764c\u75c7\u662f\u7531\u7d30\u83cc\u611f\u67d3\u9020\u6210)\uff0c\u4ed6\u7684\u7642\u6cd5\u4e5f\u4e0d\u88ab\u540c\u5115\u6240\u63a5\u53d7\uff0c\u7576\u6642\u6700\u8457\u540d\u7684\u9aa8\u8089\u7624\u6b0a\u5a01 James Ewing\uff0c\u66fe\u662f\u67ef\u7acb\u5728\u91ab\u9662\u4e2d\u7684\u4e0a\u53f8\uff0c\u516c\u958b\u53cd\u5c0d\u67ef\u7acb\u4f7f\u7528\u7d30\u83cc\u7642\u6cd5\u3002\u5f8c\u4f86\u5728\u653e\u5c04\u6cbb\u7642\u8207\u5316\u5b78\u7642\u6cd5\u7684\u8208\u8d77\u4e0b\uff0c\u67ef\u7acb\u7684\u7d30\u83cc\u7642\u6cd5\u6f38\u6f38\u70ba\u4e16\u4eba\u6240\u6de1\u5fd8\u3002\u6709\u8da3\u7684\u662f\uff0c\u5728\u8d85\u904e\u4e00\u767e\u5e74\u4ee5\u5f8c\uff0c\u79d1\u5b78\u754c\u767c\u73fe\u514d\u75ab\u7cfb\u7d71\u5c0d\u65bc\u764c\u75c7\u6cbb\u7642\u7684\u91cd\u8981\u6027\uff0c\u7d42\u65bc\u80fd\u89e3\u91cb\u7d30\u83cc\u7642\u6cd5\u7684\u6a5f\u5236\uff0c\u65bc\u662f\u5c0a\u7a31\u67ef\u7acb\u70ba\u514d\u75ab\u7642\u6cd5\u4e4b\u7236\u3002\u67ef\u7acb\u7684\u5973\u5152 Helen Coley Nauts \u6240\u6210\u7acb\u7684 Cancer Research Institute\uff0c\u81f4\u529b\u65bc\u514d\u75ab\u7642\u6cd5\u7684\u7814\u7a76\uff0c\u76ee\u524d\u7684\u4e2d\u5fc3\u4e3b\u4efb\u5c31\u662f\u767c\u73fe\u514d\u75ab\u6aa2\u67e5\u9ede CTLA-4 \u7684\u8afe\u8c9d\u723e\u734e\u5f97\u4e3b James Allison\uff0c\u7b97\u662f\u4e00\u500b\u4e16\u7d00\u4ee5\u4f86\u514d\u75ab\u7642\u6cd5\u7684\u661f\u706b\u50b3\u627f\u3002<\/p>\n

\u7d30\u83cc\u767e\u767e\u7a2e\uff0c\u54ea\u4e00\u7a2e\u6cbb\u7642\u764c\u75c7\u6700\u597d\uff1f<\/strong><\/p>\n

\u8fd1 10 \u5230 20 \u5e74\u4f86\uff0c\u7531\u65bc\u764c\u75c7\u8207\u514d\u75ab\u4e4b\u9593\u7684\u95dc\u4fc2\u6f38\u6f38\u6e05\u695a\uff0c\u7d30\u83cc\u764c\u75c7\u7642\u6cd5\u53c8\u6372\u571f\u91cd\u4f86\uff0c\u79d1\u5b78\u5bb6\u5011\u7d1b\u7d1b\u4f7f\u7528\u81ea\u5df1\u6700\u559c\u6b61\u7684\u83cc\u7a2e\u4f86\u9032\u884c\u764c\u75c7\u6cbb\u7642\u7684\u5be6\u9a57\u3002\u4ee5\u4e0b\u5c31\u5e7e\u7a2e\u6bd4\u8f03\u71b1\u9580\u4e14\u9032\u904e\u81e8\u5e8a\u8a66\u9a57\u7684\u83cc\u7a2e\u4e00\u4e00\u7c21\u4ecb\uff1a<\/p>\n

1.\u5361\u4ecb\u82d7 (Bacillus Calmette\u2013Gu\u00e9rin)<\/strong>
\n\u5361\u4ecb\u82d7\u4e0d\u662f\u7528\u4f86\u9810\u9632\u80ba\u7d50\u6838\u7684\u55ce\uff1f\u8ddf\u764c\u75c7\u6709\u4ec0\u9ebc\u95dc\u4fc2\uff1f\u5b83\u53ef\u662f\u7d30\u83cc\u7b2c\u4e00\u500b\u6210\u529f\u7528\u65bc\u6cbb\u7642\u764c\u75c7\u7684\u85e5\u7269\uff01\u5361\u4ecb\u82d7\u8d77\u6e90\u65bc\u4e00\u7a2e\u725b\u7d50\u6838\u83cc\uff0c\u81ea 1908 \u5e74\u8d77\uff0c\u4e00\u5c0d\u6cd5\u570b\u79d1\u5b78\u5bb6 Calmette \u548c Gu\u00e9rin \u8017\u8cbb 13 \u5e74\u7684\u5149\u9670\uff0c\u5728\u5be6\u9a57\u5ba4\u4e2d\u4e0d\u65b7\u5730\u7e7c\u4ee3\u8a72\u83cc\uff0c\u7d42\u65bc\u6210\u529f\u57f9\u990a\u51fa\u4e00\u7a2e\u5f31\u5316\u7684\u83cc\u7a2e\u547d\u540d\u70ba BCG\uff0c\u53ef\u4ee5\u5b89\u5168\u5730\u7576\u4f5c\u80ba\u7d50\u6838\u75ab\u82d7\u5728\u4eba\u985e\u8eab\u4e0a\u4f7f\u7528\u3002\u7136\u800c 1959 \u5e74\u4e00\u7bc7 Nature \u8ad6\u6587\u610f\u5916\u5730\u767c\u73fe\uff0c\u65bd\u6253\u904e BCG \u7684\u5c0f\u9f20\uff0c\u7adf\u53ef\u4ee5\u5927\u5927\u5ef6\u7de9\u816b\u7624\u751f\u9577\u7684\u901f\u5ea6\u3002\u9019\u500b\u767c\u73fe\u5f8c\u4f86\u884d\u4f38\u51fa\u4e00\u652f\u85e5\u7269\u53ebOnco-BCG\uff0c\u57fa\u672c\u4e0a\u5c31\u662f\u5361\u4ecb\u82d7\u7684\u6210\u5206\uff0c\u4f46\u7d93\u7531\u8180\u80f1\u5167\u6ce8\u5c04\u7684\u8a71\uff0c\u53ef\u6cbb\u7642\u65e9\u671f\u8180\u80f1\u764c\u6216\u662f\u9810\u9632\u8180\u80f1\u764c\u5fa9\u767c\u3002\u6839\u64da\u7d71\u8a08\uff0c\u8180\u80f1\u764c\u7684\u60a3\u8005\u5982\u679c\u50c5\u63a5\u53d7 BCG \u57fa\u790e\u5291\u91cf (6 \u91dd) \u7684\u7642\u7a0b\uff0c\u5176 5 \u5e74\u5fa9\u767c\u7387\u6709 50%\u3002\u4f46\u5982\u679c\u518d\u65bd\u6253 7 \u81f3 9 \u91dd\u8ffd\u52a0\u5291\uff0c\u53ef\u5927\u5e45\u4e0b\u964d\u5fa9\u767c\u7387\u81f3\u63a5\u8fd1 10%\u3002\u96d6\u7136\u90a3\u9ebc\u591a\u6b21\u7642\u7a0b\u76f8\u7576\u7684\u4e0d\u4fbf\uff0c\u4f46\u662f\u7642\u6548\u5341\u5206\u986f\u8457\uff0c\u60a3\u8005\u5011\u4e00\u5b9a\u8981\u6253\u597d\u6253\u6eff\uff01<\/p>\n

2.\u9f20\u50b7\u5bd2\u6c99\u9580\u6c0f\u687f(Salmonella typhimurium)<\/strong>
\nS.typhimurium \u662f\u4e00\u7a2e\u9769\u862d\u6c0f\u9670\u6027\u83cc (gramnegative)\uff0c\u5b83\u662f\u4e00\u7a2e\u81f4\u75c5\u83cc\uff0c\u5e38\u898b\u65bc\u4eba\u985e\u7684\u98df\u7269\u4e2d\u6bd2\u4e2d\uff0c\u6703\u5f15\u8d77\u4e0a\u5410\u4e0b\u7009\u3002\u9769\u862d\u6c0f\u9670\u6027\u83cc\u5728\u5916\u819c\u4e0a\u5e36\u6709\u5927\u91cf\u8102\u591a\u91a3 (LPS)\uff0c\u53c8\u7a31\u5167\u6bd2\u7d20 (endotoxin)\uff0c\u6703\u5f15\u8d77\u4eba\u985e\u5f37\u70c8\u7684\u767c\u708e\u53cd\u61c9\uff0c\u56b4\u91cd\u53ef\u80fd\u5c0e\u81f4\u6b7b\u4ea1\u3002\u56e0\u6b64\u8981\u4f7f\u7528 S.typhimurium \u4f5c\u70ba\u764c\u75c7\u6cbb\u7642\uff0c\u5fc5\u9808\u8981\u5148\u5f31\u5316\u5176\u6bd2\u6027\u3002\u79d1\u5b78\u5bb6\u5c07\u5176\u4e2d\u4e00\u500b\u8ca0\u8cac\u5408\u6210 LPS \u91cd\u8981\u5b98\u80fd\u6a5f\u7684\u57fa\u56e0 msbB \u5254\u9664\uff0c\u53ef\u4ee5\u5927\u5927\u964d\u4f4e LPS \u7684\u6bd2\u6027\u7d04\u4e00\u767e\u500d\u3002\u53e6\u5916\uff0c\u79d1\u5b78\u5bb6\u5229\u7528\u816b\u7624\u5fae\u74b0\u5883\u4e2d\u542b\u6709\u5927\u91cf\u560c\u5464\u7684\u7279\u6027\uff0c\u5c07 S. typhimurium \u4e2d\u4e00\u500b\u8ca0\u8cac\u5408\u6210\u560c\u5464\u7684\u57fa\u56e0 purL \u5254\u9664\uff0c\u4f7f\u5176\u504f\u597d\u5728\u816b\u7624\u5167\u751f\u5b58\u3002\u6700\u7d42\uff0c msbB\/purL \u96d9\u91cd\u5254\u9664\u7684\u83cc\u7a2e\u547d\u540d\u70ba VNP20009\uff0c\u5c0d\u65bc\u5c0f\u9f20\u7684\u6bd2\u6027\u4e0b\u964d\u4e00\u842c\u500d\uff0c\u4e14\u5c0d\u5c0f\u9f20\u7684\u816b\u7624\u6709\u826f\u597d\u7684\u6cbb\u7642\u6548\u679c\u3002\u5f88\u53ef\u60dc\u7684\u662f\uff0c\u5728\u5f8c\u7e8c\u7684\u81e8\u5e8a\u5be6\u9a57\u4e2d\uff0c 24 \u4f4d\u63a5\u53d7\u6cbb\u7642\u7684\u75c5\u4eba\u4e2d\uff0c\u50c5\u6709 3 \u4f4d\u7684\u816b\u7624\u4e2d\u80fd\u89c0\u5bdf\u5230 VNP20009 \u7684\u751f\u9577\uff0c\u4e26\u4e14\u816b\u7624\u90fd\u6c92\u6709\u6d88\u9000 5<\/sup>\u3002<\/p>\n

3.\u674e\u65af\u7279 (Listeria Monocytogenes)<\/strong>
\n\u674e\u65af\u7279\u83cc\u4e5f\u662f\u4e00\u7a2e\u6703\u5c0e\u81f4\u98df\u7269\u4e2d\u6bd2\u7684\u7d30\u83cc\uff0c\u5b83\u7684\u6bd2\u6027\u76f8\u7576\u7684\u5f37\uff0c\u56b4\u91cd\u7684\u8a71\u53ef\u80fd\u6703\u81f4\u6b7b\u3002\u674e\u65af\u7279\u83cc\u662f\u4e00\u7a2e\u7d30\u80de\u5167\u75c5\u539f\u9ad4(intracellular pathogen)\uff0c\u5b83\u6703\u5165\u4fb5\u4eba\u985e\u7684\u541e\u566c\u7d30\u80de\uff0c\u5728\u7d30\u80de\u5167\u90e8\u9032\u884c\u751f\u9577\u7e41\u6b96\u3002\u79d1\u5b78\u5bb6\u65bc\u662f\u5229\u7528\u6b64\u4e00\u7279\u6027\uff0c\u5229\u7528\u57fa\u56e0\u8f49\u6b96\u7684\u65b9\u5f0f\uff0c\u4f7f\u674e\u65af\u7279\u83cc\u8868\u9054\u4e00\u7a2e\u764c\u75c7\u76f8\u95dc\u6297\u539f mesothelin\u3002\u9019\u500b\u86cb\u767d\u5728\u4e00\u822c\u5065\u5eb7\u7d30\u80de\u5e7e\u4e4e\u4e0d\u8868\u9054\uff0c\u4f46\u5728\u4e00\u4e9b\u764c\u7d30\u80de (\u5305\u62ec\u80f0\u81df\u764c\u3001\u5375\u5de2\u764c\u7b49\u7b49) \u6703\u5927\u91cf\u8868\u9054\u3002\u7531\u65bc\u674e\u65af\u7279\u83cc\u6703\u5728\u6297\u539f\u5448\u73fe\u7d30\u80de\u5167\u90e8\u751f\u9577\uff0c\u5176\u8868\u9054\u7684\u86cb\u767d\u5c31\u50cf\u5bc4\u4e3b\u7d30\u80de\u81ea\u5df1\u8868\u9054\u7684\u86cb\u767d\u4e00\u6a23\uff0c\u6703\u900f\u904e MHC class I \u5448\u73fe\u5728\u7d30\u80de\u8868\u9762\uff0c\u9032\u800c\u523a\u6fc0 CD8+T \u7d30\u80de\u7684\u6d3b\u6027\uff0c\u9054\u5230\u985e\u4f3c\u764c\u75c7\u75ab\u82d7\u7684\u6548\u679c\u3002\u5728\u4e00\u500b\u81e8\u5e8a\u4e8c\u671f\u7684\u5be6\u9a57\u4e2d\uff0c\u79d1\u5b78\u5bb6\u5229\u7528\u4e00\u7a2e\u8868\u9054 mesothelin \u4e14\u5f31\u5316\u7684\u674e\u65af\u7279\u83cc (CRS-207) \u6cbb\u7642\u80f0\u81df\u764c\u672b\u671f\u7684\u75c5\u4eba\uff0c\u914d\u5408\u5316\u7642\u8207\u514d\u75ab\u4fc3\u9032\u5291\uff0c\u5176\u5e73\u5747\u751f\u5b58\u671f\u9054\u5230 9.7 \u500b\u6708\uff0c\u6bd4\u63a7\u5236\u7d44\u589e\u9577\u4e86 5.1 \u500b\u6708\u7684\u58fd\u547d 6<\/sup>\u3002\u96d6\u7136\u53ea\u662f\u6578\u500b\u6708\u7684\u9032\u6b65\uff0c\u4f46\u7531\u65bc\u80f0\u81df\u764c\u662f\u975e\u5e38\u96e3\u6cbb\u7642\u7684\u764c\u75c7\uff0c\u5176\u7d50\u679c\u4ecd\u662f\u76f8\u7576\u4ee4\u4eba\u632f\u596e\uff01<\/p>\n

4.\u4e01\u9178\u68ad\u83cc (Clostridium butyricum)<\/strong>
\n\u8aaa\u5230\u4e01\u9178\u68ad\u83cc\u5927\u5bb6\u53ef\u80fd\u6c92\u4ec0\u9ebc\u5370\u8c61\uff0c\u4f46\u5982\u679c\u6539\u8aaa\u5999\u5229\u6563\uff0c\u76f8\u4fe1\u8a31\u591a\u4eba\u90fd\u77e5\u9053\u3002\u9019\u662f\u4e00\u652f\u65e9\u5728 1933 \u5e74\u7531\u65e5\u672c\u7814\u767c\u51fa\u7684\u76ca\u751f\u83cc\uff0c\u5176\u83cc\u682a\u547d\u540d\u70ba CBM588\u3002\u9019\u652f\u76ca\u751f\u83cc\u9664\u4e86\u5e73\u6642\u53ef\u7528\u4f5c\u7dad\u8b77\u8178\u9053\u83cc\u76f8\u5065\u5eb7\u4ee5\u5916\uff0c\u7531\u65bc\u5176\u5c0d\u65bc\u6297\u751f\u7d20\u6709\u826f\u597d\u7684\u8010\u53d7\u6027\uff0c\u53ef\u4ee5\u9810\u9632\u6216\u7de9\u89e3\u7531\u6297\u751f\u7d20\u6cbb\u7642\u6240\u5f15\u767c\u7684\u8179\u7009\u554f\u984c\u3002\u53e6\u5916\uff0c\u8fd1\u4f86\u8166\u8178\u8ef8\u7684\u81e8\u5e8a\u7814\u7a76\u4e5f\u767c\u73fe CBM588 \u8207\u6297\u6182\u9b31\u85e5\u7269\u4e00\u540c\u670d\u7528\u6642\uff0c\u80fd\u6709\u6548\u7de9\u89e3\u6182\u9b31\u75c7\u72c0\u3002\u66f4\u4ee4\u4eba\u9a5a\u5947\u7684\u662f\uff0c CBM588 \u80fd\u5927\u5e45\u589e\u52a0\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\u7684\u53cd\u61c9\u7387\u3002\u4eca\u5e74\u4e8c\u6708\u767c\u8868\u5728 Nature Medicine \u7684\u81e8\u5e8a\u4e00\u671f\u5831\u544a\u986f\u793a\uff0c\u5728\u814e\u81df\u764c\u672b\u671f\u7684\u75c5\u4eba\u4e2d\uff0c\u5982\u679c\u55ae\u7368\u4f7f\u7528\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\uff0c\u75c5\u4eba\u53cd\u61c9\u7387\u7d04\u70ba 20%\uff0c\u7b26\u5408\u4e00\u822c\u9810\u671f\u3002\u4f46\u5982\u679c\u540c\u6642\u4f7f\u7528\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\u52a0\u4e0a\u53e3\u670d CBM588\uff0c\u80fd\u5927\u5e45\u589e\u52a0\u53cd\u61c9\u7387\u81f3\u5927\u7d04 60% 7<\/sup>\u3002\u9019\u500b\u9a5a\u4eba\u7684\u767c\u73fe\u53ef\u80fd\u89e3\u91cb\u4e86\u70ba\u4ec0\u9ebc\u904e\u53bb\u5728\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\u7684\u6cbb\u7642\u4e2d\u50c5\u6709\u90e8\u5206\u75c5\u4eba\u6709\u6548\uff0c\u7b54\u6848\u6216\u8a31\u4e0d\u5728\u764c\u7d30\u80de\u8eab\u4e0a\uff0c\u800c\u662f\u5728\u6211\u5011\u7684\u8178\u9053\u83cc\u7576\u4e2d\uff01<\/p>\n

5.\u5927\u8178\u687f\u83cc (Escherichia coli)<\/strong>
\n\u6700\u5f8c\u8981\u4ecb\u7d39\u7d66\u5927\u5bb6\u6700\u719f\u6089\u7684\u83cc\u7a2e\uff0c\u79d1\u5b78\u5bb6\u6700\u597d\u7684\u670b\u53cb\u5927\u8178\u687f\u83cc\u3002\u6709\u5225\u65bc\u4e0a\u9762\u63d0\u5230\u7684\u81f4\u75c5\u83cc\uff0c\u5927\u8178\u687f\u83cc\u672c\u4f86\u5c31\u662f\u4eba\u985e\u8178\u9053\u7684\u5171\u751f\u83cc\uff0c\u5be6\u9a57\u5ba4\u5e38\u7528\u7684 K12 \u6216 strain B \u90fd\u4e0d\u6703\u5c0d\u4eba\u985e\u81f4\u75c5\u3002\u53e6\u5916\u6709\u4e00\u652f\u5927\u8178\u687f\u83cc\u7684\u76ca\u751f\u83cc\u53eb Nissle 1917\uff0c\u53ef\u4ee5\u5b89\u5168\u53e3\u670d\u4f7f\u7528\u3002\u5728\u5c0f\u9f20\u5be6\u9a57\u4e2d\uff0c\u5927\u8178\u687f\u83cc\u5177\u6709\u6975\u4f73\u7684\u816b\u7624\u6a19\u9776\u6027\u8207\u5171\u751f\u6027\u3002\u5982\u679c\u5c07\u690d\u6709\u76ae\u4e0b\u816b\u7624\u7684\u5c0f\u9f20\u4ee5\u975c\u8108\u6ce8\u5c04\u7684\u65b9\u5f0f\u6253\u5165\u5927\u8178\u687f\u83cc\uff0c99% \u4ee5\u4e0a\u7684\u5927\u8178\u687f\u83cc\u90fd\u6703\u805a\u96c6\u81f3\u816b\u7624\u5167\u751f\u9577\uff0c\u5176\u6578\u91cf\u53ef\u9054 108\/\u514b\u816b\u7624\uff0c\u76f8\u7576\u65bc\u816b\u7624\u5167\u7684\u764c\u7d30\u80de\u6578\u3002\u7531\u65bc\u5927\u8178\u687f\u83cc\u4e26\u975e\u81f4\u75c5\u83cc\uff0c\u5728\u5176\u4ed6\u5668\u5b98\u6703\u88ab\u514d\u75ab\u7cfb\u7d71\u5b8c\u5168\u6e05\u9664\u3002<\/p>\n

\u53e6\u5916\uff0c\u5927\u8178\u687f\u83cc\u7684\u4e00\u5927\u512a\u52e2\u662f\u5bb9\u6613\u9032\u884c\u57fa\u56e0\u5de5\u7a0b\uff0c\u53ef\u4ee5\u9032\u884c\u8a31\u591a\u7cbe\u5bc6\u7684\u8a2d\u8a08\u4f86\u5c0d\u6297\u764c\u75c7\u3002\u4f8b\u5982 2016 \u5e74\u7684 Nature \u8ad6\u6587\u4e2d\uff0c\u4f5c\u8005\u5011\u8a2d\u8a08\u4e86\u4e00\u500b\u540c\u6b65\u5316\u88c2\u89e3\u7684\u57fa\u56e0\u8ff4\u8def\uff0c\u53ef\u4ee5\u9031\u671f\u6027\u5730\u91cb\u653e\u5927\u8178\u687f\u83cc\u4e2d\u651c\u5e36\u7684\u6297\u764c\u86cb\u767d 8<\/sup>\u3002\u53c8\u5982\u5728\u6700\u8fd1\u7684\u81e8\u5e8a\u4e00\u671f\u5be6\u9a57\u4e2d\uff0c\u79d1\u5b78\u5bb6\u8a2d\u8a08\u4e00\u500b\u5728\u7f3a\u6c27\u74b0\u5883\u4e0b\u6703\u91cb\u653e\u74b0\u4e8c\u6838\u82f7\u9178 (Cyclic di-nucleotides) \u7684 Nissle 1917(\u547d\u540d\u70ba SYNB1891\uff0c\u5411\u67ef\u7acb\u91ab\u751f\u81f4\u656c)\u3002\u74b0\u4e8c\u6838\u82f7\u9178\u6703\u523a\u6fc0\u5148\u5929\u514d\u75ab\u7cfb\u7d71\u4e2d\u7684 STING \u8a0a\u865f\uff0c\u9032\u800c\u4fc3\u767c\u6297\u764c\u7684\u514d\u75ab\u53cd\u61c9\u3002\u76ee\u524d\u81e8\u5e8a\u8cc7\u6599\u986f\u793a\u5b89\u5168\u8010\u53d7\u6027\u826f\u597d\uff0c\u4e26\u4e14\u9054\u6210\u76ee\u6a19\u53c3\u8207 (target engagement) \u8207\u75c5\u60c5\u7a69\u5b9a (disease stabilization) 9<\/sup>\u3002<\/p>\n

\u6211\u5011\u7684\u5be6\u9a57\u5ba4\u5229\u7528\u764c\u7d30\u80de\u4f9d\u8cf4 TNF-\u03b1 \u767c\u708e\u56e0\u5b50\u7684\u7279\u6027\uff0c\u8a2d\u8a08\u51fa\u4e00\u500b\u514d\u75ab\u6bd2\u7d20 (immunotoxin)\uff0c\u80fd\u8eb2\u85cf\u5728 TNF-\u03b1 \u8eab\u5f8c\u9032\u5165\u764c\u7d30\u80de\uff0c\u4ee5\u7279\u6d1b\u4f0a\u6728\u99ac\u7684\u65b9\u5f0f\u9032\u884c\u764c\u7d30\u80de\u6bd2\u6bba (\u5716\u4e8c)\u3002\u7814\u7a76\u5718\u968a\u5c07\u6b64\u514d\u75ab\u6bd2\u7d20\u653e\u5165\u5927\u8178\u687f\u83cc\u4e2d\u9032\u884c\u764c\u75c7\u6cbb\u7642\uff0c\u8b49\u5be6\u5728\u5c0f\u9f20\u5be6\u9a57\u4e2d\u80fd\u5927\u5e45\u5ea6\u58d3\u6291\u9ed1\u8272\u7d20\u7624\u7684\u751f\u9577 10<\/sup>\u3002<\/p>\n

\"\u3010\u5c08\u6b04\u3011The

\u25b2\u5716\u4e8c \u7279\u6d1b\u4f0a\u6728\u99ac\u7d30\u83cc\u7642\u6cd5\u3002\u6211\u5011\u7684\u7814\u7a76\u5718\u968a\u5229\u7528\u7d30\u83cc\u91cb\u653e\u514d\u75ab\u6bd2\u7d20\uff0c\u4ee5\u6728\u99ac\u5c60\u57ce\u8a18\u7684\u65b9\u5f0f\u6210\u529f\u6bd2\u6bba\u764c\u7d30\u80de\u3002<\/p><\/div>\n

\u4e0b\u4e00\u500b\u6d3b\u7684\u85e5\u7269\uff0c\u7d30\u83cc\uff01\uff1f<\/strong>
\n\u5f9e\u67ef\u7acb\u91ab\u751f 1891 \u5e74\u7684\u5617\u8a66\u958b\u59cb\uff0c\u7d30\u83cc\u764c\u75c7\u7642\u6cd5\u5df2\u7d93\u8d85\u904e\u4e00\u767e\u5e74\uff0c\u5f9e\u81e8\u5e8a\u8a66\u9a57\u5230\u4e0d\u88ab FDA \u627f\u8a8d\uff0c\u7d42\u65bc\u53c8\u56de\u5230\u81e8\u5e8a\u8a66\u9a57\uff0c\u4ee5\u73fe\u4ee3\u79d1\u5b78\u56b4\u8b39\u7684\u624b\u6cd5\u771f\u6b63\u6e2c\u8a66\u7d30\u83cc\u7642\u6cd5\u662f\u5426\u6709\u6548\u3002\u5728\u9019\u4e2d\u9593\u4e00\u767e\u591a\u5e74\u7684\u6b77\u53f2\uff0c\u4eba\u985e\u9664\u4e86\u767c\u5c55\u51fa\u8a31\u591a\u6cbb\u7642\u764c\u75c7\u7684\u65b9\u6cd5\uff0c\u4e5f\u5c0d\u514d\u75ab\u7cfb\u7d71\u5728\u764c\u75c7\u767c\u5c55\u904e\u7a0b\u6240\u626e\u6f14\u7684\u89d2\u8272\u6709\u6df1\u523b\u7684\u4e86\u89e3\u3002\u5982\u4eca\uff0c\u514d\u75ab\u7642\u6cd5\u6210\u70ba\u5b78\u91ab\u754c\u666e\u904d\u7684\u5171\u8b58\uff0c\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\u8207 CAR-T \u7642\u6cd5\u5df2\u7d93\u5728\u8a31\u591a\u764c\u75c7\u75c5\u4eba\u8eab\u4e0a\u770b\u5230\u75ca\u7652\u7684\u66d9\u5149\u3002\u7d30\u83cc\u764c\u75c7\u7642\u6cd5\u8207 CAR-T \u4e00\u6a23\uff0c\u65e2\u662f\u514d\u75ab\u7642\u6cd5\u4e5f\u662f\u6d3b\u7684\u85e5\u7269\uff0c\u800c\u4e14\u9084\u53ef\u80fd\u6709\u52a9\u65bc\u514d\u75ab\u6aa2\u67e5\u9ede\u6291\u5236\u5291\u7684\u7642\u6548\u3002\u6bd4\u8d77 CAR-T \u7684\u500b\u4eba\u5316\u7642\u7a0b\u548c\u6709\u9650\u7684\u8907\u88fd\u80fd\u529b\uff0c\u7d30\u83cc\u5177\u6709\u73fe\u8ca8 (off-the-shelf) \u4ee5\u53ca\u7121\u9650\u7684\u8907\u88fd\u80fd\u529b\uff0c\u5176\u666e\u53ca\u6027\u548c\u50f9\u683c\u90fd\u6bd4 CAR-T \u66f4\u6709\u512a\u52e2\u3002<\/p>\n

\u5728\u6cd5\u898f\u65b9\u9762\uff0c\u7f8e\u570b FDA \u8207\u6b50\u6d32\u85e5\u5178\u59d4\u54e1\u6703\u7d1b\u7d1b\u5728 2016 \u8207 2019 \u5e74\u7d66\u4e88\u6d3b\u83cc\u85e5\u7269 (live biotherapeutic product, LBP) \u7d66\u51fa\u5b9a\u7fa9\u8207\u6307\u5f15\u3002\u6839\u64da 2020 \u5e74\u7684\u7d71\u8a08\uff0c\u8ddf LBP \u76f8\u95dc\u7684\u5c08\u5229\u8d85\u904e 640 \u500b\uff0c\u76f8\u95dc\u7684\u65b0\u85e5\u81e8\u5e8a\u6e2c\u8a66 (Investigational new drug, IND) \u8d85\u904e 575 \u500b\uff0c\u8d85\u904e 50 \u5bb6 GMP \u7b49\u7d1a\u7684\u88fd\u6210\u516c\u53f8\u5728\u6469\u62f3\u64e6\u638c\u6e96\u5099\u91cf\u7522 LBP\u3002\u76ee\u524d\u5e02\u9762\u5c1a\u672a\u6709 FDA \u6838\u51c6\u7684 LBP \u85e5\u7269\uff0c\u4f46\u662f\u4eca\u5e74\u65b0\u82f1\u683c\u862d\u91ab\u5b78\u96dc\u8a8c\u767c\u8868\u4e86\u4e00\u500b LBP \u7684\u81e8\u5e8a\u4e09\u671f\u7d50\u679c\uff0c\u8a72\u81e8\u5e8a\u6e2c\u8a66\u4f7f\u7528\u4e00\u7a2e\u53e3\u670d\u7684\u76ca\u751f\u83cc SER-109 \u6cbb\u7642\u7531\u8271\u96e3\u68ad\u72c0\u82bd\u5b62\u6746\u83cc (C.difficile) \u6240\u5f15\u8d77\u7684\u611f\u67d3\u8179\u7009\u554f\u984c\u3002\u5be6\u9a57\u7d50\u679c\u986f\u793a SER-109 \u7684\u9577\u671f\u53cd\u61c9\u7387\u9054 88%\uff0c\u6bd4\u8d77\u63a7\u5236\u7d44 60% \u6709\u986f\u8457\u9032\u6b65 11<\/sup>\u3002 SER-109 \u5f88\u6709\u53ef\u80fd\u5728\u4eca\u5e74\u88ab\u6838\u51c6\u6210\u70ba\u4eba\u985e\u53f2\u4e0a\u7b2c\u4e00\u500b\u4e0a\u5e02\u7684 LBP\u3002\u8b93\u6211\u5011\u4e5f\u671f\u5f85\u67d0\u4e00\u652f\u6216\u6578\u652f\u7d30\u83cc\u80fd\u812b\u7a4e\u800c\u51fa\uff0c\u6210\u70ba\u4e0b\u500b\u4e16\u4ee3\u7684\u6297\u764c\u5229\u5668\uff01<\/p>\n

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

    \n
  • Brentjens, R.J., Riviere, I., Park, J.H., Davila, M.L., Wang, X., Stefanski, J., Taylor, C., Yeh, R., Bartido, S., Borquez-Ojeda, O., Olszewska, M., Bernal, Y., Pegram, H., Przybylowski, M., Hollyman, D., Usachenko, Y., Pirraglia, D., Hosey, J., Santos, E., Halton, E., Maslak, P., Scheinberg, D., Jurcic, J., Heaney, M., Heller, G., Frattini, M. & Sadelain, M. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood 118, 4817-4828 (2011).<\/li>\n
  • Kochenderfer, J.N., Wilson, W.H., Janik, J.E., Dudley, M.E., Stetler-Stevenson, M., Feldman, S.A., Maric, I., Raffeld, M., Nathan, D.A., Lanier, B.J., Morgan, R.A. & Rosenberg, S.A. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood 116, 4099-4102 (2010).<\/li>\n
  • Porter, D.L., Levine, B.L., Kalos, M., Bagg, A. & June, C.H. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 365, 725-733 (2011).<\/li>\n
  • Melenhorst, J.J., Chen, G.M., Wang, M., Porter, D.L., Chen, C., Collins, M.A., Gao, P., Bandyopadhyay, S., Sun, H., Zhao, Z., Lundh, S., Pruteanu-Malinici, I., Nobles, C.L., Maji, S., Frey, N.V., Gill, S.I., Tian, L., Kulikovskaya, I., Gupta, M., Ambrose, D.E., Davis, M.M., Fraietta, J.A., Brogdon, J.L., Young, R.M., Chew, A., Levine, B.L., Siegel, D.L., Alanio, C., Wherry, E.J., Bushman, F.D., Lacey, S.F., Tan, K. & June, C.H. Decade-long leukaemia remissions with persistence of CD4(+) CAR T cells. Nature 602, 503-509 (2022).<\/li>\n
  • Toso, J.F., Gill, V.J., Hwu, P., Marincola, F.M., Restifo, N.P., Schwartzentruber, D.J., Sherry, R.M., Topalian, S.L., Yang, J.C., Stock, F., Freezer, L.J., Morton, K.E., Seipp, C., Haworth, L., Mavroukakis, S., White, D., MacDonald, S., Mao, J., Sznol, M. & Rosenberg, S.A. Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma. J Clin Oncol 20, 142-152 (2002).<\/li>\n
  • Le, D.T., Wang-Gillam, A., Picozzi, V., Greten, T.F., Crocenzi, T., Springett, G., Morse, M., Zeh, H., Cohen, D., Fine, R.L., Onners, B., Uram, J.N., Laheru, D.A., Lutz, E.R., Solt, S., Murphy, A.L., Skoble, J., Lemmens, E., Grous, J., Dubensky, T., Jr., Brockstedt, D.G. & Jaffee, E.M. Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol 33, 1325-1333 (2015).<\/li>\n
  • Dizman, N., Meza, L., Bergerot, P., Alcantara, M., Dorff, T., Lyou, Y., Frankel, P., Cui, Y., Mira, V., Llamas, M., Hsu, J., Zengin, Z., Salgia, N., Salgia, S., Malhotra, J., Chawla, N., Chehrazi-Raffle, A., Muddasani, R., Gillece, J., Reining, L., Trent, J., Takahashi, M., Oka, K., Higashi, S., Kortylewski, M., Highlander, S.K. & Pal, S.K. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nat Med 28, 704-712 (2022).<\/li>\n
  • Din, M.O., Danino, T., Prindle, A., Skalak, M., Selimkhanov, J., Allen, K., Julio, E., Atolia, E., Tsimring, L.S., Bhatia, S.N. & Hasty, J. Synchronized cycles of bacterial lysis for in vivo delivery. Nature 536, 81-85 (2016).<\/li>\n
  • Leventhal, D.S., Sokolovska, A., Li, N., Plescia, C., Kolodziej, S.A., Gallant, C.W., Christmas, R., Gao, J.R., James, M.J., Abin-Fuentes, A., Momin, M., Bergeron, C., Fisher, A., Miller, P.F., West, K.A. & Lora, J.M. Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity. Nat Commun 11, 2739 (2020).<\/li>\n
  • Hu, C.W., Chang, Y.C., Liu, C.H., Yu, Y.A. & Mou, K.Y. Development of a TNF-alpha-mediated Trojan Horse for bacteria-based cancer therapy. Mol Ther (2022).<\/li>\n
  • Feuerstadt, P., Louie, T.J., Lashner, B., Wang, E.E.L., Diao, L., Bryant, J.A., Sims, M., Kraft, C.S., Cohen, S.H., Berenson, C.S., Korman, L.Y., Ford, C.B., Litcofsky, K.D., Lombardo, M.J., Wortman, J.R., Wu, H., Aunins, J.G., McChalicher, C.W.J., Winkler, J.A., McGovern, B.H., Trucksis, M., Henn, M.R. & von Moltke, L. SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. N Engl J Med 386, 220-229 (2022).<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"

    \u201cThe Good, the Bad, and the Ugly\u201d (\u4e2d\u6587\u8b6f\u4f5c\u300a\u9ec3\u660f\u4e09\u93e2\u5ba2\u300b) \u662f\u7fa9\u5927\u5229\u5c0e\u6f14\u8cfd […]<\/p>\n","protected":false},"author":1,"featured_media":28209,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_et_pb_use_builder":"","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"categories":[991,983],"tags":[],"acf":[],"_links":{"self":[{"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/posts\/28204"}],"collection":[{"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/comments?post=28204"}],"version-history":[{"count":1,"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/posts\/28204\/revisions"}],"predecessor-version":[{"id":29359,"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/posts\/28204\/revisions\/29359"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/media\/28209"}],"wp:attachment":[{"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/media?parent=28204"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/categories?post=28204"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/newsletter.sinica.edu.tw\/wp-json\/wp\/v2\/tags?post=28204"}],"curies":[{"name":"wp","href":"https:\/api.w.org\/{rel}","templated":true}]}}