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“现货型”同种异体 CAR 细胞疗法——被忽视的 HvG 效应

英文原题:"Off-the-Shelf" Allogeneic CAR Cell Therapy-Neglected HvG Effect.

查看英文原题

"Off-the-Shelf" Allogeneic CAR Cell Therapy-Neglected HvG Effect.

PubMed 2023/04/03(内容时间) Curr Treat Options Oncol Q1 · IF 5.8(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)细胞疗法为血液系统恶性肿瘤患者提供了一种新的治疗选择。传统上,使用自体T细胞为每位患者生成CAR设计的T细胞。然而,这种方法存在若干缺点,异体CAR细胞疗法的发展将是一个有前景的突破,可以解决其中的一些局限性。从已发表数据的临床试验来看,异体CAR细胞疗法的疗效未达到预期。由于宿主抗移植物(HvG)效应,异体CAR细胞被宿主清除,导致异体CAR细胞持久性短和疗效差。解决异体CAR细胞的HvG效应至关重要。目前常用的方法包括抑制宿主免疫系统、使用HLA匹配的纯合供者、降低HLA表达、靶向同种反应性淋巴细胞以及消除抗CAR活性。在这篇综述中,我们将聚焦于“现货型”异体CAR细胞疗法的HvG效应,特别是其机制和当前解决该问题的方法,并总结相关临床试验数据。

展开英文摘要原文

Chimeric antigen receptor (CAR) cell therapy offers patients with hematological malignancies a new therapeutic option. Traditionally, autologous T cells are used to generate CAR designed T cells for each patient.

However, this method has several drawbacks, the development of allogeneic CAR cell therapy would be a promising breakthrough that could address several of these limitations. From the clinical trials that have published data, the efficacy of allogeneic CAR cell therapy did not meet the expectations. Because of the host-versus-graft (HvG) effect, allogeneic CAR cells are eliminated by the host, resulting in short-term persistence of allogeneic CAR cells and poor efficacy.

It is critical to solve the HvG effect of allogeneic CAR cells. The current commonly used methods are suppressing the host's immune system, using HLA-matched homozygous donors, reducing the expression of HLA, targeting alloreactive lymphocytes and eliminating anti-CAR activities. In this review, we will focus on the HvG effect of the "off-the-shelf" allogeneic CAR cell therapy, especially its mechanism and current methods to solve this problem and summarize relevant clinical trial data.

论文信息

作者
An Y、Jin X、Zhang H、Zhang M、Mahara S、Lu W、Zhao M
第一作者单位
First Center Clinical College, Tianjin Medical University, Tianjin, 300192, China.China
通讯作者单位
Department of Hematology, Tianjin First Central Hospital, Tianjin, 300192, China. mingfengzhao@sina.com.China
文献类型
综述 · 非美国政府资助研究
期刊
Current treatment options in oncology2023 May
原文标识
PubMed 37010679 · DOI 10.1007/s11864-023-01061-8