Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells.
Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells.
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DOI：
10.1016/j.jcyt.2016.07.003
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发表时间：
2016-11
期刊：
影响因子：
4.5
通讯作者：
Brentjens, Renter J.
中科院分区：
文献类型：
--
作者：
Geyer, Mark B.;Brentjens, Renter J.
关键词：
在过去的几年里，免疫疗法的临床应用取得了非凡的进展。特别是，利用靶向CD19的嵌合抗原受体（CAR）修饰T细胞的过继细胞疗法在复发或难治性B细胞急性淋巴细胞白血病（B- all）的儿童和成人中显示出显著的临床疗效，并且在一小部分复发或难治性慢性淋巴细胞白血病（CLL）或B细胞非霍奇金淋巴瘤（B- nhl）患者中显示出持久的临床益处。早期临床试验目前正在评估CAR - T细胞在其他恶性肿瘤中的安全性和有效性。在此，我们讨论了迄今为止研究B-ALL、CLL和B-NHL中cd19靶向CAR - T细胞的最大系列的临床结果，包括CAR - T细胞设计、生产和治疗方法的差异，以及临床疗效、严重细胞因子释放综合征和神经毒性的性质，以及CAR - T细胞的扩增和持久性。我们还回顾了CAR - T细胞目前和即将在多发性骨髓瘤和几种实体瘤中的应用，并强调了CAR - T细胞治疗当前状态所带来的挑战和机遇，包括克服肿瘤微环境抑制方面和增强抗肿瘤功效的策略。
The past several years have been marked by extraordinary advances in clinical applications of immunotherapy. In particular, adoptive cellular therapy utilizing chimeric antigen receptor (CAR) modified T cells targeted to CD19 has demonstrated substantial clinical efficacy in children and adults with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL), and durable clinical benefit in a smaller subset of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or B cell non-Hodgkin lymphoma (B-NHL). Early phase clinical trials are presently assessing CAR T cell safety and efficacy in additional malignancies. Herein, we discuss clinical results from the largest series to date investigating CD19-targeted CAR T cells in B-ALL, CLL, and B-NHL, including discussion of differences in CAR T cell design and production and treatment approach, as well as clinical efficacy, nature of severe cytokine release syndrome and neurologic toxicities, and CAR T cell expansion and persistence. We additionally review the current and forthcoming use of CAR T cells in multiple myeloma and several solid tumors, and highlight challenges and opportunities afforded by the current state of CAR T cell therapies, including strategies to overcome inhibitory aspects of the tumor microenvironment and enhance antitumor efficacy.
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影响因子：
17.1
作者：
Fedorov VD;Themeli M;Sadelain M
通讯作者：
Sadelain M
影响因子：
5.7
作者：
Feng Y;Xiao X;Zhu Z;Streaker E;Ho M;Pastan I;Dimitrov DS
通讯作者：
Dimitrov DS
影响因子：
20.3
作者：
Fraietta, Joseph A.;Beckwith, Kyle A.;Maus, Marcela V.
通讯作者：
Maus, Marcela V.
影响因子：
45.3
作者：
Ahmed, Nabil;Brawley, Vita S.;Gottschalk, Stephen
通讯作者：
Gottschalk, Stephen
DOI：
10.1056/nejmoa1504542
发表时间：
2015-09-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Garfall AL;Maus MV;Hwang WT;Lacey SF;Mahnke YD;Melenhorst JJ;Zheng Z;Vogl DT;Cohen AD;Weiss BM;Dengel K;Kerr ND;Bagg A;Levine BL;June CH;Stadtmauer EA
通讯作者：
Stadtmauer EA