← 返回

嵌合抗原受体(CAR)T 细胞治疗肾移植后淋巴增殖性疾病(PTLD)患者

英文原题:Chimeric antigen receptor (CAR) T cells for the treatment of a kidney transplant patient with post-transplant lymphoproliferative disorder (PTLD).

查看英文原题

Chimeric antigen receptor (CAR) T cells for the treatment of a kidney transplant patient with post-transplant lymphoproliferative disorder (PTLD).

PubMed 2023/06/06(内容时间) Hum Vaccin Immunother Q2 · IF 4.2(JCR 2025)

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。

中文摘要

移植后淋巴增殖性疾病(PTLD)是肾移植后一种可能致命的并发症,对于与更显著和持久缓解相关的PTLD治疗存在关键且未满足的需求。迄今为止,关于在实体器官移植(SOT)后患者中使用CD19靶向嵌合抗原受体(CAR)T(CAR-T)细胞的报道仅为个案,临床表现和结局异质性大,且尚未有PTLD患者中CAR-T 细胞扩增和持续存在的纵向分析报道。

我们的报告描述了一名有肾移植病史的患者,其接受了CD19导向的CAR-T 细胞治疗,用于治疗难治性PTLD,弥漫性大B细胞淋巴瘤(DLBCL)型。

我们表明,即使在SOT长期免疫抑制的背景下,也有可能生成能够在体内扩增和持续存在的自体CAR-T 产品,且没有过度T细胞耗竭的证据。

我们的数据表明,从患有PTLD的SOT受者生成的CAR-T 细胞可以实现深度缓解,而不增加毒性或同种异体肾功能障碍。未来的临床研究应基于这些发现,探索CAR-T 治疗用于SOT受者PTLD,包括对CAR-T 表型和功能进行纵向监测。

展开英文摘要原文

Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication following kidney transplantation, and there is a critical and unmet need for PTLD treatments associated with more pronounced and durable responses.

To date, reports on the use of CD19-targeted chimeric antigen receptor (CAR) T (CAR-T) cells in patients after solid organ transplant (SOT) have been anecdotal, clinical presentations and outcomes have been heterogenous, and a longitudinal analysis of CAR-T cell expansion and persistence in PTLD patients has not been reported.

Our report describes a patient with a history of renal transplant who received CD19-directed CAR-T cell therapy for the treatment of refractory PTLD, diffuse large B cell lymphoma (DLBCL)-type.

We show that even with the background of prolonged immunosuppression for SOT, it is possible to generate autologous CAR-T products capable of expansion and persistence in vivo, without evidence of excess T-cell exhaustion.

Our data indicate that CAR-T cells generated from a SOT recipient with PTLD can yield deep remissions without increased toxicity or renal allograft dysfunction. Future clinical studies should build on these findings to investigate CAR-T therapy, including longitudinal monitoring of CAR-T phenotype and function, for PTLD in SOT recipients.

论文信息

作者
Kline K、Chen W、Kallen ME、Koka R、Omili D、Fan X、Iraguha T、Gebru E
单位
University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.United States
文献类型
非美国政府资助研究 · 美国 NIH 资助研究
期刊
Human vaccines & immunotherapeutics2023 Aug 1
原文标识
PubMed 37278257 · DOI 10.1080/21645515.2023.2216116