波士顿CAR-TCR 峰会回顾： 一群渴望改变世界的勇者
在依依不舍的惜别中，为期两天的CAR-TCR峰会在美国波士顿落下了帷幕。诺华公司的CAR-T产品刚刚获准上市，最近Celletics公司CAR-T试验又被紧急叫停，本届CAR-TCR峰会开幕之初充满了诸多戏剧性的看点。大量精彩的成果展示、小组讨论，让渴望了解CAR-TCR行业的人们大饱眼福。
笔者也非常赞同现场一位嘉宾的观点：致力于CAR-TCR行业的医生、科学家、工业界专业人士是一群渴望改变世界的勇者。
EP Vantage高级记者Jacob Plieth在此次峰会开幕致辞时回顾了数十年来CAR-T疗法的发展历程，他总结了CAR-T技术获得成功的三个关键词：带有共刺激结构域的CAR、CD19和B细胞白血病、宾夕法尼亚大学儿童急性淋巴性白血病临床试验中的“1号病人”--艾米丽。
CAR-T技术似乎已经经过了很长时间的发展，但前路漫漫，仍有诸多未知：对于投入巨资的药物开发者来说，CAR-T在商业上是否可行？CAR-T生产能否量产？除了 B细胞血液肿瘤之外，CAR-T技术针对其他肿瘤是否也能达到治愈艾米丽这样的疗效？第三代CAR, 第四代CAR，装配CAR,双靶点CAR, 基因敲出的TCR, 安全开关等等诸如此类的新产品，哪个才是最终可以攻克实体瘤的超强武器呢？异体CAR-T细胞的前景又如何？
当被记者Plieth问及收获了哪些惊喜或失望时，Novartis, Juno, Bluebird Bio, Ziopharm, Adaptimmune 和Cellectics的业界领袖回答都大同小异，而Sunil Agarwal（Juno研发总裁）的回答让人印象深刻，“担心CAR-T研究中可能出现的二类错误会让我经常睡不着觉。”（注：二类错误是指在进行假设检验时，原假设不正确而接受原假设的错误）
尽管有许多会议内容值得关注，但由于大会时间限制，整个峰会同时设立了临床前研究、转化、生产制备、商业化四个分会场。与会嘉宾同一时间只能参加一个分会场，对于时间冲突的报告，没有录音或录像供会后回放。
TCR被广泛地预测为最有希望突破固体肿瘤治疗的技术。TKI药物和CAR-T联合用药的治疗方案展示出了减少细胞因子风暴的潜力。在CMC工艺小组讨论中，与会专家还深入探讨了CAR-T细胞自动化生产的必要性以及自动化生产过程优化时机等问题。哈佛大学附属丹娜法伯癌症研究院（Dana-Farber Cancer Institute）在大会现场展示了一项非常深入的研究成果，这项耗时两年才开发出来的细胞疗法方案将有效解决CAR-T产品商业化后的医院管理标准等问题。
正如一位发言嘉宾所言，CAR-T技术从学术发现向工业研发转移并不意味着研发结束，而是CAR-T研发新的开始。同样，首个上市的CAR-T药物也只是对过去20年CAR-T研发努力的肯定，Gilead收购Kite也表示了对细胞治疗产业价值的认可。我们还有很长的路要走，不过这一次我们有了更多的知识和更大的勇气！
Two days CAR-TCR Summit comes to the endwith the crowd in the mood of unwilling to leave, followed its opening at adramatic moment, when clinical hold was put on Cellectis trial due to the fetalCRS event shortly after the announcement of FDA approval granted to the firstin Class CAR-T therapy launched by Novartis.
Informative presentations and insightfulpanel discussions nicely fulfilled the know-how eagerness and sharing wellnessof this innovative and courageous group of people. Quite agree with the commentfrom one panelist that, doctors, scientists or industrial professionals whohave committed to the CAR-TCR development are the ones who want to make achange to the world.
Jacob Plieth, Senior Reporter from EP Vantage, reviewed decades development history of CAR-T therapy atopening remarks, pointed out the three keys to today CAR-T success:co-stimulated CARs, CD19 and B-cell malignancies, and "patient 1" inPenn's pediatric ALL study.
Looks like we have come a long way, yet there arestill so many unknowns down the road: will CAR-T Therapy become profitable forthe deeply invested drug developers? Can manufacturing be scaled? when themoment of Emily Whitehead will come for other cancers beyond B-cellmalignancies? Among 3rd generation CAR, 4th generation CAR, armored CAR,bispecific boolean-logic CAR, genetic knockout TCR,switch receptors, etc, which one will be the supercharged CAR with "bells& whistles" that can conquer the solid tumors eventually? What aboutallogeneic products?
When asked for surprise and disappointmentby Plieth, industrial leaders from Novartis, Juno, Bluebird Bio, Ziopharm,Adaptimmune and Cellectics gave various yet consensus in context responses,with a vivid answer from Sunil Agarwal that the concern on potential Type IIerror in CAR-T development is one thing wakes him up at night.
Many talks worth to highlights and recap,yet the limitation of the event is with four parallel streams specified fordiscovery, translation, manufacturing and commercialization and many greattopics, no audio record or video is available for the attendees who can onlyattend one stream at one time.
TCR is emerging as the next thing with theanticipation for solid tumor breakthrough. Combination of TKI with CAR-T showsthe potential for minimizing the CRS risk. How much automation is truly neededfor CAR-T manufacturing and when is the right time doing the automationoptimization were widely discussed at CMC panel. Dana-Farber Cancer Institutepresented a very comprehensive and impressive Engineered Cell Therapy Program,which took two full years development, to cover the Hospital managementstandards following the commercialization of CAR-T Therapy.
As one presenter mentioned, the moment whenthe CAR-T Therapy moves from academic discovery to industrial development, itis not the end of developing but the starting point. Similarly, the firstapproval of CAR-T therapy officially endorsed the people's efforts over lasttwo decades, Gilead purchase of Kite confirmed the value of this sector, yet westill have the long way to go, but with better knowledge and more courage.
11月17日国际细胞治疗上海峰会，30多位国际顶级的药政专家、临床KOL、知名企业C-level高管、投资人、顶级律所专利律师，将从技术、生产、监管、知识产权、企业融资发展等各个角度为大家带来精彩主题分享。会议详情请见：全球CAR-T专家齐聚上海，共演细胞治疗巅峰盛会。