Mechanisms of resistance to CAR T cell therapy.
Mechanisms of resistance to CAR T cell therapy.
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DOI：
10.1038/s41571-019-0184-6
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发表时间：
2019-06
期刊：
影响因子：
--
通讯作者：
Fry TJ
中科院分区：
文献类型：
--
作者：
Shah NN;Fry TJ
嵌合抗原受体（CAR）T细胞疗法在涉及前B细胞急性淋巴细胞白血病（ALL）或B细胞淋巴瘤患者的早期临床试验中的成功已经彻底改变了抗癌疗法，为标准治疗难治的患者提供了潜在的治愈选择。这些试验导致FDA快速批准抗CD 19 CAR T细胞产品用于ALL和某些类型的B细胞淋巴瘤-这是美国首批批准的基因疗法。然而，使用这些药物的经验越来越多，表明由于抗原丢失或调节导致的CAR T细胞持久性差和/或癌细胞耐药性，大量患者的缓解将是短暂的。此外，CAR T细胞的初步经验突出了与制造患者特异性疗法相关的挑战。了解CAR T细胞疗法的局限性对于实现这种新型治疗方法的全部潜力至关重要。在本文中，我们讨论了可以排除CAR T细胞治疗后持久缓解的因素，主要关注疾病复发的耐药机制。我们还提供了一个潜在的策略，以克服这些障碍，努力更有效地将这种独特的治疗策略纳入标准的治疗模式的概述。
The successes with chimeric antigen receptor (CAR) T cell therapy in early clinical trials involving patients with pre-B cell acute lymphoblastic leukaemia (ALL) or B cell lymphomas have revolutionized anticancer therapy, providing a potentially curative option for patients who are refractory to standard treatments. These trials resulted in rapid FDA approvals of anti-CD19 CAR T cell products for both ALL and certain types of B cell lymphoma — the first approved gene therapies in the USA. However, growing experience with these agents has revealed that remissions will be brief in a substantial number of patients owing to poor CAR T cell persistence and/or cancer cell resistance resulting from antigen loss or modulation. Furthermore, the initial experience with CAR T cells has highlighted challenges associated with manufacturing a patient-specific therapy. Understanding the limitations of CAR T cell therapy will be critical to realizing the full potential of this novel treatment approach. Herein, we discuss the factors that can preclude durable remissions following CAR T cell therapy, with a primary focus on the resistance mechanisms that underlie disease relapse. We also provide an overview of potential strategies to overcome these obstacles in an effort to more effectively incorporate this unique therapeutic strategy into standard treatment paradigms.
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影响因子：
11.4
作者：
Cooper ML;Choi J;Staser K;Ritchey JK;Devenport JM;Eckardt K;Rettig MP;Wang B;Eissenberg LG;Ghobadi A;Gehrs LN;Prior JL;Achilefu S;Miller CA;Fronick CC;O'Neal J;Gao F;Weinstock DM;Gutierrez A;Fulton RS;DiPersio JF
通讯作者：
DiPersio JF
影响因子：
11.4
作者：
Bhojwani D;Sposto R;Shah NN;Rodriguez V;Yuan C;Stetler-Stevenson M;O'Brien MM;McNeer JL;Quereshi A;Cabannes A;Schlegel P;Rossig C;Dalla-Pozza L;August K;Alexander S;Bourquin JP;Zwaan M;Raetz EA;Loh ML;Rheingold SR
通讯作者：
Rheingold SR
影响因子：
28.4
作者：
Ahmed N;Brawley V;Hegde M;Bielamowicz K;Kalra M;Landi D;Robertson C;Gray TL;Diouf O;Wakefield A;Ghazi A;Gerken C;Yi Z;Ashoori A;Wu MF;Liu H;Rooney C;Dotti G;Gee A;Su J;Kew Y;Baskin D;Zhang YJ;New P;Grilley B;Stojakovic M;Hicks J;Powell SZ;Brenner MK;Heslop HE;Grossman R;Wels WS;Gottschalk S
通讯作者：
Gottschalk S
影响因子：
20.3
作者：
Braig, Friederike;Brandt, Anna;Binder, Mascha
通讯作者：
Binder, Mascha
影响因子：
7
作者：
Daher M;Rezvani K
通讯作者：
Rezvani K