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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Rapid response in relapsed follicular lymphoma with massive chylous ascites to anti-CD19 CAR T therapy using Piggy Bac: A case report.
Rapid response in relapsed follicular lymphoma with massive chylous ascites to anti-CD19 CAR T therapy using Piggy Bac: A case report.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
CD19靶向嵌合抗原受体(CAR)T细胞疗法已被证明在难治性或复发性B细胞非霍奇金淋巴瘤患者中可实现相当持久的缓解,Zuma-1、Zuma-5及其他临床试验结果均显示了这一点。这些CAR大多通过慢病毒或逆转录腺病毒制备。使用非病毒载体(如Piggy Bac,pb)的CAR用于治疗活动性疾病的淋巴瘤患者较为罕见。一般而言,如文献报道,高肿瘤负荷的患者往往有更高的严重细胞因子释放综合征(CRS)或神经系统事件发生率。有症状性胸腔积液的患者因存在严重CRS风险而被排除在Zuma-1试验之外。
我们在此报告一例复发性滤泡性淋巴瘤患者,伴有大块病灶和大量乳糜性腹水,多线化疗失败。在输注CD19靶向pbCAR-T 细胞6×10^6 cells/kg后,患者迅速获得缓解,并在第28天达到近乎完全代谢缓解。仅发生1级CRS,未出现神经毒性。CAR-T 细胞在第14天达到峰值水平,并扩散至腹水中,持续扩增3个月。这可能是首例报道的pbCAR-T 细胞直接治疗复发性滤泡性淋巴瘤的病例。长期疗效有待观察,未来将有更多患者接受测试。临床试验注册:https://ClinicalTrials.gov,标识符NCT05472610。
UNLABELLED: CD19-directed chimeric antigen receptor (CAR) T cell therapy has been shown to achieve a considerably durable response in patients with refractory or relapsed B cell non-Hodgkin lymphomas, as seen from the results of Zuma-1, Zuma-5, and other clinical trials. Most of these CARs were generated by lentivirus or reverse adenovirus.
It is rare to see CARs using non-viral vectors, such as Piggy Bac (pb), in treating lymphoma patients with active diseases. Generally, patients with a high tumor burden tend to have a higher rate of severe cytokine release syndrome (CRS) or neurological events as reported in the literature. Patients with symptomatic pleural effusions are excluded from the Zuma-1 trial because of the risk of severe CRS.
We report here that a patient with relapsed follicular lymphoma with bulky disease and massive chylous ascites failed several lines of chemotherapy. After infusion of the CD19-directed pbCAR-T cells at 6 10 6 cells/kg, the patient had a rapid response and achieved a nearly complete metabolic remission on day 28. There was only grade 1 CRS, and no neurotoxicity occurred.
The CAR-T cells reached a peak level on day 14 and spread into the ascites and expanded for 3 months. This might be the first case reported for pbCAR-T cells to treat relapsed follicular lymphoma directly. The long-term efficacy will be observed, and more patients be tested in the future. CLINICAL TRIAL REGISTRATION: https://ClinicalTrials. gov, identifier NCT05472610.
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