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Chimeric antigen receptor T-cell therapies for lymphoma
Nature Reviews Clinical Oncology ( IF 81.1 ) Pub Date : 2017-08-31 , DOI: 10.1038/nrclinonc.2017.128
Jennifer N. Brudno , James N. Kochenderfer

New therapies are needed for patients with Hodgkin or non-Hodgkin lymphomas that are resistant to standard therapies. Indeed, unresponsiveness to standard chemotherapy and relapse after autologous stem-cell transplantation are indicators of an especially poor prognosis. Chimeric antigen receptor (CAR) T cells are emerging as a novel treatment modality for these patients. Clinical trial data have demonstrated the potent activity of anti-CD19 CAR T cells against multiple subtypes of B-cell lymphoma, including diffuse large-B-cell lymphoma (DLBCL), follicular lymphoma, mantle-cell lymphoma, and marginal-zone lymphoma. Importantly, anti-CD19 CAR T cells have impressive activity against chemotherapy-refractory lymphoma, inducing durable complete remissions lasting >2 years in some patients with refractory DLBCL. CAR-T-cell therapies are, however, associated with potentially fatal toxicities, including cytokine-release syndrome and neurological toxicities. CAR T cells with novel target antigens, including CD20, CD22, and κ-light chain for B-cell lymphomas, and CD30 for Hodgkin and T-cell lymphomas, are currently being investigated in clinical trials. Centrally manufactured CAR T cells are also being tested in industry-sponsored multicentre clinical trials, and will probably soon become a standard therapy. Herein, we review the clinical efficacy and toxicity of CAR-T-cell therapies for lymphoma, and discuss their limitations and future directions with regard to toxicity management, CAR designs and CAR-T-cell phenotypes, conditioning regimens, and combination therapies.



中文翻译:

嵌合抗原受体T细胞疗法用于淋巴瘤

对标准疗法有抵抗力的霍奇金或非霍奇金淋巴瘤患者需要新的疗法。实际上,对标准化学疗法的无反应性以及自体干细胞移植后的复发是预后特别差的指标。嵌合抗原受体(CAR)T细胞正在成为这些患者的一种新型治疗方法。临床试验数据表明,抗CD19 CAR T细胞对多种亚型B细胞淋巴瘤(包括弥漫性大B细胞淋巴瘤(DLBCL),滤泡性淋巴瘤,套细胞淋巴瘤和边缘区淋巴瘤)具有有效的活性。重要的是,抗CD19 CAR T细胞对化学疗法难治性淋巴瘤具有令人印象深刻的活性,在一些难治性DLBCL患者中诱导了持续> 2年的持久完全缓解。但是,CAR-T细胞疗法是 与潜在的致命毒性相关,包括细胞因子释放综合征和神经毒性。目前正在临床试验中研究具有新型靶抗原的CAR T细胞,包括针对B细胞淋巴瘤的CD20,CD22和κ轻链,以及针对霍奇金淋巴瘤和T细胞淋巴瘤的CD30。集中生产的CAR T细胞也正在行业支持的多中心临床试验中进行测试,并且可能很快会成为标准疗法。本文中,我们回顾了CAR-T细胞疗法对淋巴瘤的临床疗效和毒性,并讨论了它们在毒性管理,CAR设计和CAR-T细胞表型,调理方案和联合疗法方面的局限性和未来发展方向。目前正在临床试验中研究具有新型靶抗原的CAR T细胞,包括针对B细胞淋巴瘤的CD20,CD22和κ轻链,以及针对霍奇金淋巴瘤和T细胞淋巴瘤的CD30。集中生产的CAR T细胞也正在行业支持的多中心临床试验中进行测试,并且可能很快会成为标准疗法。本文中,我们回顾了CAR-T细胞疗法对淋巴瘤的临床疗效和毒性,并讨论了它们在毒性管理,CAR设计和CAR-T细胞表型,调理方案和联合疗法方面的局限性和未来发展方向。目前正在临床试验中研究具有新型靶抗原的CAR T细胞,包括针对B细胞淋巴瘤的CD20,CD22和κ轻链,以及针对霍奇金淋巴瘤和T细胞淋巴瘤的CD30。集中生产的CAR T细胞也正在行业支持的多中心临床试验中进行测试,并且可能很快会成为标准疗法。本文中,我们回顾了CAR-T细胞疗法对淋巴瘤的临床疗效和毒性,并讨论了它们在毒性管理,CAR设计和CAR-T细胞表型,调理方案和联合疗法方面的局限性和未来发展方向。集中生产的CAR T细胞也正在行业支持的多中心临床试验中进行测试,并且可能很快会成为标准疗法。本文中,我们回顾了CAR-T细胞疗法对淋巴瘤的临床疗效和毒性,并讨论了它们在毒性管理,CAR设计和CAR-T细胞表型,调理方案和联合疗法方面的局限性和未来发展方向。集中生产的CAR T细胞也正在行业支持的多中心临床试验中进行测试,并且可能很快会成为标准疗法。本文中,我们回顾了CAR-T细胞疗法对淋巴瘤的临床疗效和毒性,并讨论了它们在毒性管理,CAR设计和CAR-T细胞表型,调理方案和联合疗法方面的局限性和未来发展方向。

更新日期:2017-09-19
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