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标题:CAR-T细胞疗法 未来肿瘤治愈的新希望
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发表于 2018-5-4 16:45 资料 个人空间 短消息  加为好友 
CAR-T细胞疗法 未来肿瘤治愈的新希望

2018年4月份,国内两家CAR-T细胞产品临床试验申请完成技术评审,一个是上海生物公司恒润达生的抗人CD19 T 细胞注射液(受理号为CXSL1700193),另一个是银河生物的抗人 CD19分子嵌合抗原受体修饰的自体 T 淋巴细胞注射液(受理号为CXSL1700122)。新药临床试验IND申请,是一项作为药物上市的关键性研究,上海生物医药公司美迪西的IND申报服务平台深入了解中国和美国法规政策环境以及其对化药的技术要求,能为国内客户提供CFDAIND申报,USFDAIND/ANDA申报服务,能为国外客户提供CFDAIND/ANDA申报服务。


2017年1225日,上海恒润达生生物的“抗人CD19T细胞注射液”临床试验申请正式被CDE受理,这是继南京传奇生物之后,第3个通过药品申报路径提交并获受理的第3CAR-T细胞治疗临床试验申请。20184月显示,该申请已经完成技术审核。


银河生物的这款产品于去年1215日向国家药监局申报临床申请,本次联合提交的临床试验申请的适应症为淋巴瘤,该产品因此也成为国内首个申报CAR-T疗法治疗淋巴瘤新药临床试验的细胞治疗类生物制品。


1、什么是CAR-T细胞疗法


CAR-T细胞疗法,即嵌合抗原受体T细胞免疫疗法,是一种细胞治疗方法,它是在T细胞上加上一个嵌合抗原受体嵌合抗原受体“GPS导航(胞外抗原识别区)和激活按钮(胞内信号转导区)组成, 而CTL019或者说CAR-T 019,实际就是加上了一个可以识别肿瘤细胞表面“CD19”的一个抗原受体,当“GPS导航定位到肿瘤抗原并与之结合,之后激活按钮就开始激活T细胞,从而对肿瘤展开杀戒。


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ftBiGaISIZEYqw4JEYP417Fewyyadcx2uFmaF1iI4wxBx9Oa5eT4exv8AEAeLf7TcSBg3keWMHC7cZrsxQB40PCHxb2jGu44/5+v/AK1avi7w7Z6p4X0qx8R69BYazax8SzPuEhPXPqM969SyK5Pxl4FsPGdpGlxI1vcQE+VOgyR7EdxQB55fD4i+CNLS7uL621HTIyoHmESqM9ODzVb4j65J4l8F+H9VjtzBBJJIssSn5RIAOn4ZrbHwZ1ScJb3/AIrkms1IxEEY4+gJxXdSeCNGl8LJ4cMJNkigLk/Orf3gfWgCz4cn05vCdjJbyRfZVtVyQRgDHOf1ryX4YfP4z8SSWf8Ax5m2m5HTBb5a2T8FdSiD2tp4qljsXPMRQ5I+gOK7fw54I07wxosunWBYvOpE1w/LOSMZ/wDrUAeT/DNJW8O+M1hB3m2wMdf4q6D4DTWS6RqUW6NbzzwXB4Ypjj8M5rqPBfw+j8GNfFdQa8W9ChleMLjGfz61g6p8GopdUkvdE1mTThKxJiCEhc9QCD0+tAHPfG+SxfxRpQt2Q3Sx/wCkFOuNw25/WpfjRze+Fh/0xP8ANK2ZPgdaywwM2t3DXKsWlmdA2/pgAZ4xj9a3vGHw5XxbLpskmpvb/wBnx7FAjDbuRyfyoA88+KkV0/jvRgsqwg2cIhlk+6rbjyfxxWtrvhv4gz6LMuteKNO/s91Hmea4CkfXbXeeK/Atj4t0mC0u3Mc9uMQ3KDlTjnjuD6Vxw+DOqXJS21HxVNLYp0iVWzj2ycUAZGqaRNo3wTks5b22vF+2iSKS2k3LtOOM/XNdx8JbOC3+HthKkaq85dnbHLHeRz+Aq1q/w9stQ8IR+GrOc2NtEysGVdxOPXPUk1q+F/Dw8NeHbXR1uTcLb7sSMuCcsT0/GgDk/iboWia79kiudat9M1GL/UeYeHBPQj6965XUrj4ieBrSO6v7u31LT1KgecRKv055FegeNvh7Y+MoopJJmtbyEYjnQZ49CO4rlE+C+o3Lxw6p4qmuLND/AKpVbOPbJwKAPQPCutReIvDlnqsUHkC4TJiHRSDgge2RW0KpaVpdto+m2+nWcfl29ugVFq9QAUUUUAFFFFABRRRQAUUUUAFFFFABRRRQAUUUUAFFFFABVLU9Sh0qxnvbgN5MC7nKrk4+nertNaNGzuUEHqDQB5lofxOOu2msQSjyLuMSmzMUTY2KpILE8A+1J4a+Kml2vhqxOuX01xfuCZ5ViJC5JxuIGBWb4ZvY9N/4S7Rbq2nivbqaaSEeScFdh706y06OL4B3CrZbbiSNi48v52bdwT3zQB3+seNNI0S3tZLiR5XvFDQRQIXeQeoA7VL4f8V6Z4khlawdw8B2yxSqVeM+4NeWavZXNnqHhvWbi5v7OwOlRwm6tI9zwOF5BB6A10Pw7so5fEGpavb3Wp3aSqIzdXkaos/uAOcigDstf8W6R4ZNv/as5hFySsbBSRketUNI+Iug6zqkenQSTQ3EozELiIp5n0zXNfGAiO+8NObY3Oy8LeSBkyYwcVW1bUB428W+H00fTbqI6fcCa4nlhMYjUEZX9KAOlufip4ZtriW3aad5oZjC0aQsTuBwatav8QdF0e9FlL9onuggd4beIu0Yxn5sdKwPhhZR/wBreJria1AdtQbY7pyVyehPaqVnqcHgfxzr8uu20+zUJBJbXKRGQMv92gDtIvHGhzeHW15bxBZJwzEEEN/dx1z7Vxni/wCJ0dxp9mPD95cWty92gYSQ7TJEeCRuHSuYuNA1S88JahrENhMtrPqq3UdmVO4xDOTj8av+O/Eum+KrPSE0nTrlmgukZ5DblfKGR8mf89KAPVbPxFp93rl1osEjNd2ahplK4AB9+9UG8UeHr+01N55I3t9OcpdefH8qt6c9a5GbVl8I/FDWb6/sruSK/gQW5hiLhyB0rmotP1TW/Cfil4rGWOY6mly1sVO5lHVffr+lAHcaP4q8EXeoxw2umRWc8oJgkksxH5uP7pxzVfTvijbXPi+fTZFK2JAW3dYW3mQnHzeg61Jp/jLSNZm0jT7Lw/NeXUYUOZINos8AAnJFUft8Hh74v6hLfWk/lX1ukUDJCWDNkd+1AG34c8RRQWetX2qeIPtsFnclCzw+WIP9gf3jVvTfiToWpX0NoDPbNcHED3ERRZT7E15x/ZGoah4O8TLbW8skkWtidogpzKgHOB39fwrV8Q63beNoNC0jQrC4N3BdRyys0JQWwUYIz/npQB2OofE3w5pt5c2c08pubV9jwrESxPt61t6B4g0/xLpov9Nm82EsVORgqw7EVxHgmyQ/ELxdcXFsCysixO6djndgn1wKs/CCJ4dN1xHiaMf2rIVDLjjavSgDpPEfjDSfDDQx30jtPP8A6qCJS7v9AKxZfFvhLWdNuNRu7dZ/sPEkE9tuliJ/2TzzWT4qY+Hvija+I9QtpJtMe08kSpGX8l+e3b1pvhrdr/xC1fxJZ2ksOltaeUrSx7POYDBOD9KAKPgDxRqPiLxCfteuXMaiR/K09LcCIxAcfNjjHp7V2njvxK/hXw497boJbqRxFAp6bz3P0rE+DsDp4e1ESwFG/tGQjeuDjAq/8UdBu9Z8MKdPiMtxZyrOsQ6vjtQBiyad8SrCxi1ePXl1C5+V307yQFIPYH2rpfF3ie40LwLLqbRG2vpIlWOLO4pK3b3wa5ub4qNNpccGl6PeSa221DbywEKrd+fSqvjaLWfFWt6B4b+W2uFj+03UioWiikxkD3xQBsfDzXtal1G/0HxJcme/gRJ43YAbkYA449M1jy6h4p1fx3rml2fitdKtrFl8tZI1YHI6DNVdRsPEfhDxto+vatqP9qLK/wBmlkih27UPYgfWpbTwjp/ib4k+JhqtvM0SlGidHZBk8E5HWgDe+HHiPV9UvdX0vVrqO/bTpQiXkagCTOeOOtbvirS/EGorbLoOtf2WyMfNYxh9/p1rjfBmn3Vn/b/gZppbR4yXtb1Ew2wnqD3PSur8N+E9Q0LUHurvxJfaorx7BFcH5VORzQBwvh1vH/iLUNUs4/F/lHTZ/JdjAp3nPUccdK9Zjd7a0Tz5AzIg8yRuAcDk1wfwyikTxF4sLxsqvfEqWUjcMnpXaa/aS3ugX9rAcSzW7on1I4oA54/FTw2LkxGWfyQ/l/ahEfJ3f71X9c8daPoNzDaytLcXEyb0htozI231wO1cJ4d8U6ZpXg+28OXugz3WpQv5b2LW+RI27O7JGKr69azaX49n1LULvUdHtLy1TybiyiD+XjH7s8HHTtQB0/i/xsLn4eXOt+Hr14pYpkTdtwyHOCpB+tQ6d4i1T/hZFtp1xfubBtJW5kjYDbv25LZxXI3WnZ+HWv3doNRuFvbuJg91EFaXa33wBzzmtu3ic/E2B2tZJYzoIDIFI3fu/u59TQB08fxQ0B7lYwLoQPL5SXRgbyWbOMbq7EEMMjkHvXgcOoPpMaQ+GbvVUuRc/wDIFu7bzEXnnnFe8WrO9rE0qhJCg3qOgOORQBLiloooAKKKKACiiigAooooAKKKKACiiigAooooAKKKKACiiigAooooAKKKKACiiigAooooATauc4GfpSbRjGBinUUANKgjBUEemKFUKMKAPanUUAYeueGLPX7zT7u6aVZNOm82EIQAT71squB0AJ68U7FGKAAADoAPpSMqt95QfqKWigAxxjHFN8tB0RR+FPooAaVHcA49qNoHQCnUUANCKpyFAPsKCoJyVBI9RS4ooAQKB0AH0pAiryFAJ64FPooAaFAOcDNKAB0GKWigBrKrjDKGHoRShQowAAPQUtFACAAdBiloooAbsUNuCjPrjmjAznAz606igBpAPUA0YA6ACnUUAN2jOcDNLS0UAIAB0AFGKKM80AN8td27aufXHNKVBGCAfqKXNLQA3aMYwMemKNoznAzTqaWxQAnlru3bVz645pwGKN3FGaAFopCcUA5FAC0UmaNwoAWikBzS0AFFJRmgBaKTNGaAFopM0UALRRRQAUUUUAFFFFABRRRQAUUlFAC0UUUAFFFFABRRRQAUUUUAFFFFABRRRQAUUUUAFFFFABRRRQAUUUUAFFFFABRRRQAUUUUAFFFFABRRRQAUUUlACMcCuWm1fUJNRu/Lu7a3gtZhGUlH3xgZOe3WupIyKx7jw7YXd79rmj3TA5DUFxa6nNJ43uxp2Lq2aKYq0kUwwQ4WQIeO3UVaPxCkDkLokzIEkkD+ao3JG21jjtyRiuhPh7SZI0R9PhZUUqoI6AnJ/UA0/wDsHS8Y+xRY2MnT+Fjlh+JoIZzh+JFoZLgpp9w8MKsRIBwxXqDxgdeOaV/GN1Dqhtp7FxNLFCYLXev3nLYy/wBBW6fDOi+bJKdNh3yLtY4OCO/H4CpLzQtLvt5urKKUyIqMSDnCnK8+2aAKWpa5JZ+H2v5IRDMVAEZYNhicY461k23jeVNOtz9iN5dOJd4jYIB5YySc+1dFJotk1nDaRwrHDAQY1UcLimRaDp6TvM9usksmQzP1wRg/mKRenKcw/jq6mnkP2TybZHtyj8MxWQE8j8O1Tv8AEeGFEebTZFWeETQbZA5dS20ZA5BroG8OaQZUmGnwiVFVVbB4C/d/Ks2x8DaRZ3FxM0RuGuE2MJAAAM54x70ySk3xDAt/NXSLjCRNLOGYL5aqwUnnr14qbxLr99Y3Nuto21HgaVsRbzwMjPoK24/D2kR25gSwiEbRmNlIJypOSD6880+40q3uJVkIKsiGMY/unqKCotJ6nPL49jt7iK1uLSSRkiRriWLlUJTd+WO+aWXx68Gm217NpUii9K/ZVWQMZAwyCccrx7Vsx+GtJimhn+wxNLAoVHbOQB09jSL4U0FYXhXS4VR2DHGQcjpg5yOvakSzHX4gxuryrpc/kwpE87M4Vow7bR8p5JBqKy8dX0wkjl0gNcCacIiTADy4+pye/tWqnhHRU1I3hs0ZgsaxqR8sYTpgfjVqfwtodzvM2mxMZJDIx5BLHqevfv60xFPQfFZ8Q3Ev2SxdbWLbmd2HJKhgNv410Kncuar2un2ll5n2W3jhEhBbYMZIGB+gqzjFABRRRQAtFFFACHoawG12ystRv7m/vY7e3tysKb2+82MnA6k8jpW+elYmtW2nada3evyWMUtzaW7OJGXJ+UE0AaWn6lZ6rai6sbhJ4WOAy+vp9atVwXwtt7ix8LTatqcu19Tna7be2FUHv7Zrs7PUbXUIjLaTxzRhtpZGBGfSgC1WRfeJNNsNQFhcSuJygkIWNmCp/eYgYA46mtbORWXcaHazX1xeygu9xbfZnXPBTJP9aAMe48faMIYJLcXFz5tykGFhYFS3RsY6enrVmPxvojRF0lnYeYYlC2zkyMM5CjHzYwc46VjjR/DVjbNZtqEkTpeIQejpIgJA4HZcnNIJPCraVarb6pMn2W4cwSRZModwS2BjJBBPbpQBvnxhozW7TRXYYBkRRsPzMwJUdOnB59qhtPGulzoFd5POWISyiOF2VARkc47jpWBA/g9NWwsk0badahA7K21w+QD05b5iB9Tip7KHwotrLpFtqE7nU1Rdqht4C/KOg4x3zQBs6f4ts9V1a0tLIGSOdJSzspVkaMjKkH/eroh0rntH8H6do15HdWzzGSMyEbm4+fG7j8BXQjigBaKKKACiiigAooooAKKKKACiiigAooooAKKKKACiiigAooooAKKKKACiiigAooooAKKKKACiiigBKTFOooAQUUVhnxhoI1X+zP7Tg+1FtgTPVvTPTNA1FvY3KyNV8VaJotwLfUNQiglKhthySBnGTjpWkZPTp7V4f8Qo5T421FbjgTRoYi3Qrtxx+OaluyNqFL2kuU9U8ReMdK8NQwS3Zkl+0cosC7jt/vH25rT0zVLPVbCK+sp1mt5l3I4/rXims63DrdhpiG1kinsojEzsQVYcdPyzXWfCuW4j8GakYIjI0d1KYAehO0YA/Gkp3ZvVwjpwUmegtq+nJerYvfQLdMMiEuNx/CrBlQck4rwjQLyC28Txanr4mZ42Z2OCSsvuOvrWnpnizWrzxxay/aJTHd3Bj+y5yqxn29hzmlzomWFnFX6Hs4IPSjHNQ/aIkZUaRAzfdBYAn6VKGya0OMdRRRQAUUUUAFFFFABRRRQAtFFFABVe+tIb+xns7hd0U8bRuvqCMGrFJQBy1n4Nit0givr+a+tbVAlvbSACNVHTIH3j9ar+F5U0/U9Ut7wm3ub2/Z44ihC7cYXaenIGcV2OAe1UNR0+O+MIckeRMkyY/vL0/nQBeHSkYZFcJq3jXV7bWL20g09YoLUY86bJ3E424A65PasbRfE+q2d9dXEl9PfzbGZ7KdNm3v8AIRkH6UaBqdxd+E9OvdWm1GYOzzQNC0efl5GC2P72OM1nQeAbO1EZt765iuIX3xzpgMvy7cYxg8Vs+HdZTXdGh1BI2jEnVW7EdfqK1KAObuPB1tdTNK1/dK5SIbgQfnjOUf61Y0bwraaTqDXqTTS3EkbLI8hHzlm3EnHfNbuBQBigBQAKWiigAooooAKKKKACiiigAooooAKKKKACiiigAooooAKKKKACiiigAooooAKKKKACiiigAooooAKKKKACkJxS00jIoA881j4jTWPjNNLMUS6aJfInlbO8Ej73sMmuE8SaMuk6vPbeb5kRPmwyZ5wcnr7V2HjzwLf3mqSalpVst0k+DPBu2sG9Rng1zU/gfX7XR5L64tcKow0G4tIqev8A9asZczPWwvsoa33N+Txvcw+HYNJuXkivpbMFrxedjHlcjvkDkj1qPwDa/wDCUrew63At/DalTDNNy6MQcqD1I6GoNBg0Dxaba21Uvb6jbRCIeXJsW4jHQ/UfnVPR49T8NeM72PwtKuoaY/EhnYiNW9M92HqKtK+xy1JRp7GJ4psotB1/VNOhJMcOHjH91WGcfhXs3g3To9M8IafaooX9yGfHdm5JryXxlZ3x1qTUr0QuNQjCsIAcK6jGOeenNdRpOrahF4f+22ut3M8UMXEZReqjlcY/CpSszavN1KUTl9VMmqeK9TS2wxe5k2k9AidT+ldX8P7Pw5CV1KK5kn1GUMIknwHwvXYoPGffmua8HPdi9l1G2t4JnMbFknJCsXPIyOhxWt4QtrXw7qM19rGi3IuWmZ7eWAiWKBD24OfXnFEYX1ROIxD5FBmS9wdZ1U6lrd08Bnn2tIMgWsYPQY6dOfevWrjxBp9hob6jHOlxDHEHQI4JkHQY+vrXkmv61Fq1/q2qWcapasPIgXbjzSM5cj1Ofyqx4X0S71hYrCJlDxQq8ssgOIx0UY703JrQ8ZVGm0d34X8eS67d3Nleaf8AYp7ZPMLb9yMuevtVC6+L2mwagtvb2FxdQtJ5fmx4yx9VXqRSaj4Qm0jwjrksEzT389qVLqu0BByVUfTPNed+GNWg0nU4NVa0FyUiKxpu27G9elDny7np4XDutFtbn0LG++NX/vAGnV4tp/i/xRrXjLTbe3vSnmzgyW8YzGsQ+9n8O9e0A81SaauY1Kbpy5WLRRRVGYUUUUALRRRQAUUUUAFVdRhknsbiOGRo5WjYI6nlWxwatUmKAPJtXg1RYI21WORrnHmSRoclzjCnI9O/1qjbrPcXkCWrx28a4Zs8uir1JPTnp+Jr0fUvDH27W01A3kiwbNs1ueQ3oVP8JFZGk+FL1vENzcakIzp68W8JcuzHszH+lQ4Xdy1O0bF3wfeXcqz2bWLRW1uF2SsCN7MSTj2AxXUjpSIoUYHA9BTsVZAtFFFABRVHVtXttGsnu7st5aDooyWPYAetN0nV7bWtNh1C13eTMMrvGCOccigVzQoqlZatZai0q2dxHN5LmOTY2SrDqDVzNAxaKSloAKY5IGRT6ZIwRcnpQBXtbzzJpoJQEkjbp6qehp91dJaw+YwzlgoHqScCoLi3Q3cVzvCMmR/vA9jWFd+OtBg10aHPKwuEb52dMIhAzyaAOpaVFUszABeST2psFxFcxiSJtyNyD61i3d/oupPBYyajE3n/ADLHHMP3uOxx1HtWxGFiXHyqoAAA4AoAlZ1QZYgAdzSCRGUMrBgehBzXH/Ei6nTw7HHbuyxXFwkc7p2j5J5HQEgD8awvB3i/T9F0hrC7juVm3tIpI3K2TgBOaTZDkkz00MD0pwrz34e6lqF7r+oi7upJg8SylWORGxYgADtxjj2r0IUFLUWiiimMKKKKACiiigAooooAKbuB71S1nVoNF0ye/ucmOFckL1Y9gPcmuN8La/4g1zxC0k1xClkgJltgg/d5+6AepPqaCXJJ2PQKWud1/wAZ6b4aubaG+EhE55dBkRr03N7Vu29xFdQpNC6yRuoZWU5BB6Ggd0S0UUUDCiiigBKjlK+W24gADnNSVyfj/UxaaKliJ1gk1GQQeYzAbE6ufyotcL2POvFVtZG7m1fREeO1Euzf/C0meXT0XjBq94Y8QC4RrS8FvE6ECMxfKJcjnj1yK2oXsPsyWlqFlhVdu1RuGPesd/CsJ1FLqGXyoQ4cw7eh9j2FNU3F3R2UpRrR5Zk/iyKWfSgYrcMUkBJ6sq9zVPRbGS68M3NtveD7RIxVwMZHHP06iujAzkH9aZNPBbxl5ZFjUd2OBWnJrc6YNRhymVoWjT6VHIJJlIcjCR9B7/WtK7SSWznhjlw0kbKCR0JFZF54ktUZFtxdz7jtUQQZ3N6An+lV5tf+zYaVtQsyDyLu0yg+pH+NFklZGFVxm9THutE1GGzsrd7by4YiBIQcknueO3+Ndh4bfUtCtpLy3jjlac7pbRhhto+6obs2Pw5qG01f7Ra/aN1vgceaso8s+47/AIVUl8S2VtMTJqkXH3vKgLKB9ahQRySoJO6J/FXxDOtWaaPosNws9ywjuI2XbIueNgHqfX0plp8KNVe2Vp9Ut7RsZEaQl9n45Gao6oiahJD4k8N3ULarZfMwTH70DqCK3P8AhcFjPpUMkdlI14U/fRswRI27jPespx6s3o1px92GhnWOv+H/AAZeSxaVp8l/cRExz30jhSxB5xx0r1DR9Ug1jTIL+33COddyhhgivBtOvLNdW+031mtxGXaX7KCVXJOQBnqBXWaP4/1yXxDZ23kQG1mlWIWkMfKIe+726+lRF62N8RQfLzI9cBpaYKcK2POFooooAWiiigAooooAKKKKAEI4poRQcgU+igBBS0hOKwNc8X6bosv2Zma5vW+5awfM5+voPrQB0FJXAXGv+KtRH7r7LpER9B50uP5Cs59Hkueb3WtVun/vG7KfouBVKDYmzrvGuj3OtaMIbW5S3khkEwaRcq2AeD7c15ppes6npFtPFbXLQJKE3BOVVvmLFQemcCtm60x7DT5prC81ATIhwv2hpN/qCG4NYBSYRxQvbOhnkLIGU5IACgEfmaiUHc56knfQ9A8DeHbnSJbm+umQNeqmEQ5zjJ3N7812dYuk63Y3JjtQxhnQBfKkG0nHceorZyPWna25vDYWlpBS0FEVxPFawPPM4jjQZZm6AVn22v6XqE/2e3u0mcnhQDz+NabKrqVcBlPUEZBpuyNQNqKPoKAOA8fyaidVsLaKZreyCNO8qPhgU5P9PzrmkmwEkgZRJLyFZFZE7gMcZJxVrxnHqlp4vnudSM8mi3EZiEg5SBWAGfbkc1j22m3yuzPC7p5wkS7tGDBxjsOlZ1FJ7GlJQv7xes9J0vxB4h02QCS1aV3hm8g7dkijcP5GvUrxLGLEuo3BKIBhZZMDjvjua4Gy02KTT3ysluWm81GVijoRwGz6/wCNX0Cqo8yWS5f/AJ6Snc351vCDauzJ76GrrfizRodEvhC+5xbt5aGMgMcYA5968s+yyCe0giYmUBIVPo7cdP8AgX6V22qfZLixktryQRRygDcXCkHsR75rK/4Rq3mmglW+kMQcSOR952B4IYdPwpSp32MZRbdz0jw/4dsPDlr9ns0O5uZJWOXkb1JrZFedWetXmkXX2W21db0n/l1vJdz/AEV+ufY12GiazBq0Dsm6OaM7ZYX+8jf4e9LlaNUa1FJS0igoopMgUALSHgGjI9ay9c1mx0XT2ur68W1Q/KrMM8+w70AJqesnT8qse9tu7JOB6fU/gKzbDVNSvrpQLtyrNniwKIB/d3E5/Gubh8QahdXjXWkadFcQnhL3UmPmN/ur2X2omtbzULj7TqupXElwfurbytFHGPQAH9TzVKLFc7DXBpGqWkmlajeRR+cQNnmhXBByCPevJrDUJNN1VNRtZg0kU0kRcnAmjXP3gOvaugv9GtY9FuUt7RbicRMVaT55JG9Sx5Jrj7e1ktIbSORSkSpxvXDO/U4H14qJJ30MJ6nSW2n674oRrxojdsB5btK4VQTyVA9BXo/hPSZND8O2mmyyCR4EwSDxyc4HsOlZ/gH7PF4at7YSg3CAtcIfvI7HJBFdOMdqErF042Q+ikpaZqFJS0UAYfivXj4d0Ka+SLzZtyxQR/35GOFH515vNbfZHh1DxEW1bVLx9iLIfkjOC21R0AGOtdp8SJLaDw8lzPMqtbXcUsaHrIQfugeuM1x2t3RnnETxxz20sPmRBEJlQ8fP+HoMVrBaGcmX7DUopPIje0azafLImQQccnp+dX59yxFl6rzj19aydLiN68NzKxkSEh4nwoy2MdBzwPU0viDV00+AWsYeW8ulKQRoMn0yfYVoaU7pmohDoGXowyKZJBFOVE0aSBTkBxkA+tJao0VpDG5yyoAT6nFSg80j0lsYg1q10zxZaXZQ3EECtE8a4+QtjDr2JHQjrUREKXV5Kl/e6pJexvEBPGVjUMerepHbFaVzo2n3MxlltU3nqy8E1ZhgihXEUaoPYUrEez1uZy+HtNWJnjsIROU4JXjdjjI6VVsUu28OWunaNe2lrqHmN/aX2sKHJ7Y3DG36dq6Dvmsu+0RJ5XuLecwzNjIZRIjfgen4UrBKFyG88NWEutvdWsohuFjjDXVn8gaYD5iB0IPp0qhFZ6P4X8UjUdYshfRXSbtyJxDIPvNs6EHr7c1uWUUkVoY5JGc5B3FQufoB0qDVFWbxLpETAMu2ZmXGeMYoscVVcjO2uvD/AIe8S2EE0tpBcQOoeKVOOD3BFS6N4S0XQmd9Ps1jd+rklm+mT2rD8CEabNf6N5pESS+baRP/AAxnqF9ga7YVi1ZgqkmrXADFLRRQSFFFFAC0UUUAFFFFABRRRQAUhIAyaWmyMqIWY4VRkmgDkvGfiG6tnh0XRzjUrxSxl7W0fdz79hXPabptvpkbJApeVjmWeX5nkbuc1XsLo6xqWo64c4vJjHCfSFOBj6mtWtEjelT5tWNILEkkn60BQOcDFLSirOlU4roULrUZYbjybKyubtl/1hhGUj4z8xPQ47VaW+UWgumUlNm/OMEexpjWUDSvKUIZwA21iu/HrjrUskUc0JikQFCu0r2IoMpUFIpR3V/ewwNqOkS2KTSMkMhf51YcgjuBjvXbeGtUfULeSO4I+1WreXN78ZVvoRXH29jHaFHR5pPLG1fOlZ9i+i56VpaRdfYfFFsS2EvYjCw9WHzKf5ilJXRxyg4Ssd0KWmr0p1YDEYEqQOtZ81neT3Xz3AW1Xny0+859CewrRpKYFO8W2Syma8EZt1QtJ5oBXaOuc15xpDW8st1fWFl9h064cfZoBn5gP48fw59K6T4iXT/2Vb6RFnfqkwibHaMcv+grLIUbUjUKiKFAHYelaQWhUI8zsG4sSW5HYGjljyeKSlxmrO+NNRVh9pFNd6RI1jaWV1qEd1snS5UMBF7Z9sH86y57cWza1Bp6qsIc/ZhEflBK/Nt/4Fmp59PtbiYSyw5cDBYMVJHocGrEaJEixxoERRhVHQUWMvY3ZVnisptBdbOeyFv9jURR7B9qW4GOScZznNWbG4k07xTo12W2i8Bs7gDoxK7l/Jh+tL5Sb94RQ397HNVNWZobCO4Unfa3MUob6OM/oTU20MKtPk1PTgafTFIKgjoeRT6yMhKz9WvZLVIUt4/NuJn2Rx5xn1J9gK0DXParcSLq5EUJaZLYRwk9C0j4/TZmgCPXfFA0nR4bq1tmu7i6fyreIcbn56n0GK4+DS5pL46prNw17qMhztLHy4R6IvQemat3VxHqHiBEiUNa6HG0CSg/62dgNxA9un1JqYD1OT61tBGlOnzsdk4C5AH+zxUN1PFa20ksgysaFyAMkipaz9Vsp7sp5DAZVo3BPBU1R1ezjFbF2XTrsS2FvJrcdneX6F4bf7NvXgZwW69KqRy3c8yWQton1ITNGVYZRSh5fPULjn8aLXxTr1skdmdKgupYf3cN1ICGVemTxz+BGadA1xosi6mGFzcIzvcs/Hmbz8361Fmc3sn2I/PvYbiC+ijh87cTBc2s2+Ofb96NvqAetek6bexajp8F7D/q50Dr7Z7V52NStLy3trGxsoLG1hlMvlxNklznPH1JNbng67Frf3Wk4IRx9ohGeFzwwHpzz+NQ0zN03Hc7KlpFOVBpakQUlLSUAef+KoRqHjqCO4BaCwtPNiQ/d8xmxu/ACpAqrg7R7cdKu+OhbwNYzLlby6m+yRsnUqwJOfpjNZ8KGKBEY8ouODxW9PY56m5XtrG3sjKYI9gkcuwznms9beBPFc8zJumltEKMf4VBwcfmKbqHi3SrGQwrI9zcdBDChLE0zR7e7u72XWb+IwSSxiKG3P8Ayyjznn3NUddBXaNkUtJRQegOzTaKKQwpcUlKOlACEdB6nFZCM1x46YLgraWYVz6MxyP5VqTXEdrbzXUrYjt0Lv8Ah2rH8GgXWnz6tJgzX87SN6qOgX6YoPLxMrs0NbuX0u0XWYmKT2DrID/eXIDKfYg16VG+8K3ZgDXl/i0J/wAIzeGU/u1UM+TgEAgkfj0/GvSNKukvdMtbqIEJNCrqD2BAxWU1ZmVN6FyiiioNQooooAWiiigAooooAKKKKACud8fXz6f4I1OeNirmLylI6guQuf8Ax6uirnvHdk9/4M1GGPO8RiRQO+xg2P0oA5TT7NbGyt7RBhYIlXHvjn9as02O4S5jiuFOVmjDg/hn+tPNbnbQa5RtFFFBuFFFFAAehqK9ZoUtLhPvw3MTKfT5gD+hNSNypA6moNSUyNYWynLT3cSqAeuDk/oKb2ODEvVHpS+tOpidD9adXMZC0lLSUwOC8VTfaPHljbHJW1snlx2yzYB/Q1E3Erj3q740tns9a0/WRnyGU2s5H8O45Un2zxVKRSJfqMcetbQ2KpO1QSilpKo9MKKKKQC1n682NAuv+mjIi/UsAKv5OcAZPYVRvIv7Q1rRtEQ7/OuRcTgdo4/mJP44pPRHHiWtj0yBSsEat1CgH8qmpg55p9YnMJWbq6urWskS5dZePTOCBn2rTprDPagDzDSopItNiSXAn3v549JNx3D86u4qfVrE6dr08Wf3V6Tcxk9Q/G9T+YIqEEFcit1sdWHa2EopaSmdYYGc4/CggHPv2oooAYkMUXMcUaf7qgZq1oGT4yjXgAWkmfflagJAGTVQak2i6sdREfm+RagEf78ign6CpnscuIa2PTV6U6mp9wc596dWJyBSUtJQBxfj+Mx3OiaiQTHbXhSQ9lDqVDfnj86hA5ArrNX02LV9MuLCcfu7hCpI7eh/A1wLte29pPpl0fKv4YyqyHpKOgdT3/oa1hKxjODb0K1uPtut3N7GsZt4YxBGQMlmDZY59O1aQIPTNZtmU021+0WUU0mkoQkxIy1tJ3Jx1Q9c9q0V8uVBLCwdG5BQ5B+lXe500KnJox1JR+n1ps0qwRNK+di8sR2HrTPQUk9h1FIjpKivGwdGGVYHINO4oGJQemByT0FHLcJyf5VWuZ5ku4tOsYjPqFwuYxjhV7s3oBQc1WtbSO5n6vbPruo23huB9scn+kX8o/5ZxDnn0zV7RVR4Z7xE8tLyUyIoG0LGPlQAdvlArqNJ8KQ6To95bpJ5l7exuJ7xx8zsQR+Q7CuY0PfFpaWVyvlz2P8Ao0yk8bl4z9CMH8amLTZ5tS9h2qxLfSafpxx/pt7GhB/uqdx/QY/GvSERUAVFCqBgADAArh/Ddr/bPiBdTwGs9P3JC/Z5TwSPUAcZruh1rObuy6ashaKKKg0CiiigBaKKKACiiigAooooAKZIoZCCAR3zT6QjNAHnU2nNompSaW+fs0jGWyc9MZyUz6jPT0NPz14x6122paVa6ra/ZrtN8edw7FT2IPY1yGoaRqGkMS0UmoWg6SxD97GPdf4vqPyrWMk1Zl05uDK/eiooLuC5OIbiNyOq5ww+oPSpgr/3CR2IqzsjXi0JRUc1xFbkedNFFn/npIFqhJ4i0aOTy2vlmkH/ACyt1MjfkBQTKtFLQ1UXec9VB/OpPDFudZ8QnUQP9C07dFGx6SzH7xHso4z65qnY2OqeJ3WGK1uNM01v9ZczLskkX+6i9Rn1Nd/YadbaZZxWlpGI4YV2oo7CpnJWscMm5yuyyKWiisQFpDS0lAytfWUOo2ktpcxrJDMpV1PcVwEttPpF1/ZeoSFuT9kuW6Sr6E/3x+tekYqpqGmWup2z215EJYn6g9j2I9DVRlYVtbnDlipw+B6ehoHNXr3w1qmnKTpsi31v2gnbEij0Dng/jWLHcXT309kNEvvPttvmpFtYLkZB681tzJnTCu1oy50FG4DHPXpWdLrMMUhhGn6nNOP+WK2jhs/iMfrVa4ufEMtzYQf2b/YtpqE3kJdXWGcMRkfIOhOOM0roHiH0L2p6tbaNAHlPm3Up229unLyMegUf1rf8FeG7uzafWdYC/wBq3ihSoORBH2QfzNWdA8C6Xo0v2yTfe6g2N11cHcwP+z/dH0rpVQLnHes3K5ztuTuxQMCnUmKWoAKKKKAOZ8Z27tYrqEQzJYEybcffUjDD8jWCOFDKMowDDvjNegSRrICrAEEYIPcVxd94Z1PTpHl0iSOe0X5hZuMOPZXJx9Aa0jKwJuLuipRWbNr9hbyNHefaLKdR80E0DBvwA6/hTB4j0kgMbzZn+/Eyn8iKu6OyNeNtTVpMjGc8Vmv4j0VFZv7WgJAzgHJ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'%s')


2、CAR-T细胞疗法


传统的肿瘤治疗方式:化疗、放疗及其近年如火如荼发展的单克隆抗体、小分子抑制剂等在肿瘤患者治疗中的巨大差异及较高的复发率,正面临着严峻的挑战。20Gross及其同事首次证明基因修饰的T细胞在对抗肿瘤细胞中的效果,从而奠定了CAR-T细胞治疗的基础。


3、T细胞治疗现状


T细胞过继治疗首次用于人体肿瘤的是应用捐献者的淋巴细胞(DLI)回输,用于一名骨髓移植后复发的髓性血液肿瘤患者,进一步的研究证明扩增的肿瘤浸润细胞(TIL)能够使大的血管转移性的黑色素瘤得到完全的、持续的缓解,对血液中循环肿瘤细胞(CTC)的监测也表明ACT治疗取得临床效果,然而此类治疗主要依赖于内源性的T细胞组份。


近来的技术发展表现在:采用逆转录病毒或质粒载体来修饰的基因工程T细胞技术,通过大量的靶向T细胞(CARTTCRT)的产生来攻击肿瘤细胞。


截止到2015年底,全球共有近8000名患者入组clinicaltrials注册的200多个临床试验,约85%的临床试验在美国和中国开展,大约65%的研究为靶向血液型肿瘤,CD19仍然是通用的血液型B细胞肿瘤的靶点抗原。目前在研的其他靶点抗原主要包括:CD20CD22CD30ROR1k轻链、CD123CD33CD133CD138等。


4、影响CAR-T细胞治疗的疗效的因素


临床数据表明在T细胞的扩增与持续存在,是CAR-T治疗中获得肿瘤有效清除的关键因素,除此之外:CAR-T的设计、回输中T细胞组成比例、肿瘤类型、肿瘤微环境和患者的预处理情况都影响着后续的治疗效果。


Savoldo及其同事采用第一代和第二代CAR-T细胞的混合组份治疗6名淋巴瘤患者证明了引入共刺激分子信号的重要性,临床试验表明包含CD28分子的CAR-T经历快速的扩增,但随之下降,而4-1BB分子信号能够使CAR-T持续存在。


在淋巴瘤的鼠动物模型中研究发现,CAR-T细胞中初始T细胞的组份不同,呈现出来的治疗效果不同,病毒转导的记忆性T细胞呈现更好的扩增潜力,


对于实体瘤的治疗,挑战依然巨大,它们所处的微环境不利于T细胞的生长,从而导致T细胞在此环境中无能。



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