CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Strategies following failure of CAR-T-cell therapy in non-Hodgkin lymphoma.
Strategies following failure of CAR-T-cell therapy in non-Hodgkin lymphoma.
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几种 CD19 CAR-T 细胞药物已获批用于晚期 B 细胞癌症的安全性和有效性,结果令人鼓舞。然而,原发性难治和复发很常见。我们批判性地分析了来自临床试验的 CD19 CAR-T 细胞疗法治疗 B 细胞非霍奇金淋巴瘤的长期疗效数据,并与所谓的真实世界数据进行比较。我们识别与疗效相关的协变量,讨论复发机制,总结失败后治疗结果的数据,包括异基因移植、单克隆和双特异性抗体、抗体-药物偶联物、免疫检查点抑制剂以及重复输注 CAR-T 细胞。我们得出结论,除异基因移植外,几乎没有数据强烈支持任何这些干预措施。大多数试验受试者数量少、治疗异质性大、干预措施多样且随访时间短。干预措施需要根据 CAR-T 细胞失败的原因进行定制。目前,对于初始 CAR-T 细胞治疗失败的 B 细胞非霍奇金淋巴瘤患者,尚无令人信服的安全有效疗法。
Several CD19 CAR-T-cell drugs are approved for safety and efficacy in advanced B-cell cancers with encouraging results.
However, primary refractory and relapse are common. We critically analyze long-term data on efficacy of CD19 CAR-T-cell therapies in B-cell non-Hodgkin lymphomas from clinical trials with those of so-called real world data.
We identify co-variates associated with efficacy, discuss mechanisms of relapse, summarize the data on the results of post-failure therapy including allotransplants, monoclonal and bi-specific antibodies, antibody-drug conjugates, immune checkpoint-inhibitors and repeat infusions of CAR-T-cells.
We conclude, save for allotransplants, there are few data strongly supporting any of these interventions. Most trial are with few heterogeneously-treated subjects with diverse interventions and brief follow-up. Interventions need to be tailored to the cause(s) of CAR-T-cell failure. Prestly, there is not a convincingly safe and effective therapy of people failing initial CAR-T-cell therapy of B-cell non-Hodgkin lymphoma.
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