Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts.
Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts.
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DOI：
10.15252/emmm.201607485
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发表时间：
2017-09
影响因子：
11.1
通讯作者：
Buchholz CJ
中科院分区：
文献类型：
--
作者：
Hartmann J;Schüßler-Lenz M;Bondanza A;Buchholz CJ
嵌合抗原受体（CAR）T细胞疗法与检查点抑制一起被誉为突破性技术，因为在复发性或难治性B细胞恶性肿瘤患者的临床试验中观察到了实质性获益。在这篇综述中，我们提供了迄今为止在全球范围内进行的临床试验的全面概述，并分析了靶向抗原和适应症，CAR分子设计，CAR T细胞制造，抗肿瘤活性和相关毒性等参数。到目前为止，已经启动了200多项CAR T细胞临床试验，其中大部分旨在使用CD19特异性汽车治疗淋巴瘤或白血病患者。越来越多的研究也涉及实体瘤。值得注意的是，迄今为止，并非所有的临床试验都显示出有希望的结果。事实上，在少数患者中，CAR T细胞治疗导致了具有致命结果的严重不良事件。值得注意的是，在欧洲进行的CAR T细胞临床试验不到10%。从我们的分析出发，我们讨论了阻碍CAR T细胞有效临床开发的问题和一般障碍以及机会，特别关注欧洲阶段。
Chimeric antigen receptor (CAR) T cell therapy, together with checkpoint inhibition, has been celebrated as a breakthrough technology due to the substantial benefit observed in clinical trials with patients suffering from relapsed or refractory B‐cell malignancies. In this review, we provide a comprehensive overview of the clinical trials performed so far worldwide and analyze parameters such as targeted antigen and indication, CAR molecular design, CAR T cell manufacturing, anti‐tumor activities, and related toxicities. More than 200 CAR T cell clinical trials have been initiated so far, most of which aim to treat lymphoma or leukemia patients using CD19‐specific CARs. An increasing number of studies address solid tumors as well. Notably, not all clinical trials conducted so far have shown promising results. Indeed, in a few patients CAR T cell therapy resulted in severe adverse events with fatal outcome. Of note, less than 10% of the ongoing CAR T cell clinical trials are performed in Europe. Taking lead from our analysis, we discuss the problems and general hurdles preventing efficient clinical development of CAR T cells as well as opportunities, with a special focus on the European stage.
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影响因子：
11.5
作者：
Kershaw, Michael H.;Westwood, Jennifer A.;Hwu, Patrick
通讯作者：
Hwu, Patrick
第一阶段的肝免疫疗法用于转移研究的动脉内嵌合抗原受体修饰的T细胞疗法用于CEA+肝转移。
DOI：
10.1158/1078-0432.ccr-14-1421
发表时间：
2015-07-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Katz SC;Burga RA;McCormack E;Wang LJ;Mooring W;Point GR;Khare PD;Thorn M;Ma Q;Stainken BF;Assanah EO;Davies R;Espat NJ;Junghans RP
通讯作者：
Junghans RP
DOI：
10.1056/nejmoa1609783
发表时间：
2017-03-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Kantarjian H;Stein A;Gökbuget N;Fielding AK;Schuh AC;Ribera JM;Wei A;Dombret H;Foà R;Bassan R;Arslan Ö;Sanz MA;Bergeron J;Demirkan F;Lech-Maranda E;Rambaldi A;Thomas X;Horst HA;Brüggemann M;Klapper W;Wood BL;Fleishman A;Nagorsen D;Holland C;Zimmerman Z;Topp MS
通讯作者：
Topp MS
影响因子：
8.8
作者：
Fitzgerald JC;Weiss SL;Maude SL;Barrett DM;Lacey SF;Melenhorst JJ;Shaw P;Berg RA;June CH;Porter DL;Frey NV;Grupp SA;Teachey DT
通讯作者：
Teachey DT
影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M