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骨肉瘤与横纹肌肉瘤 CAR 治疗的现状

英文原题:Current landscape of CAR-therapy for osteosarcoma and rhabdomyosarcoma.

PubMed 2025/11/27(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

骨肉瘤(OS)和横纹肌肉瘤(RMS)分别是儿童中最常见的骨和软组织肉瘤亚型。

中文摘要

骨肉瘤(OS)和横纹肌肉瘤(RMS)分别是儿童中最常见的骨和软组织肉瘤亚型。靶向治疗方法的缺乏以及转移情况下普遍不良的预后,使得为这些疾病发现新型治疗方式成为迫切需求。嵌合抗原受体(CAR)疗法已成为一种创新的癌症管理策略,在血液系统恶性肿瘤的治疗中取得了显著成功。该特定方法利用基因工程,通过外源性表达完全合成的受体来重定向免疫细胞(主要是T细胞)的特异性,最终使其具备识别肿瘤相关抗原(TAA)的能力。过去几年中,针对OS和RMS的CAR治疗已在临床前研究中得到探索,而最近首次临床试验的有希望结果也已发表。然而,由于各种限制因素,如CAR-T细胞向肿瘤的迁移不良、肿瘤浸润极少以及体内持久性降低,CAR疗法在实体瘤中迄今有限的疗效仍需得到妥善解决。在这篇小型综述中,我们聚焦于OS和RMS中探索的最新CAR治疗策略,同时简要回顾CAR多年来的演变,并强调CAR领域存在的挑战。

展开英文摘要原文

Osteosarcoma (OS) and rhabdomyosarcoma (RMS) are the most prevalent pediatric sarcoma subtypes of the bones and soft tissues respectively. The lack in targeted treatment approaches alongside the generally dismal prognosis in the metastatic setting render the discovery of novel therapeutic modalities for these diseases a pressing need. Chimeric antigen receptor (CAR)-therapy has emerged as an innovative strategy for cancer management with marked success in the treatment of hematological malignancies. The specific approach employs genetic engineering to redirect the specificity of immune cells, primarily T cells, through the exogenous expression of fully synthetic receptors, eventually arming them with the capacity to recognize tumor associated antigens (TAA). CAR-based treatment for OS and RMS has been under investigation in pre-clinical studies over the past few years, while the first promising results from a clinical trial have recently been published. However, the so far limited efficacy of CAR-therapy in solid tumors due to various constraining factors, such as poor CAR-T cell trafficking to the tumor, minimal tumor infiltration and reduced in vivo persistence, still needs to be properly addressed. In this mini review we focus on the most recent CAR-therapy strategies explored in OS and RMS while we briefly review the evolution of CARs through the years and highlight existing challenges in the CAR field.

论文信息

作者
Stavrou M、Nicolaou T、Georgalli M、Constantinidou A
单位
Department of Translational Research and Precision Medicine, Cyprus Cancer Research Institute (CCRI), Nicosia, Cyprus.
文献类型
综述
期刊
Frontiers in immunology2025
原文标识
PubMed 41394804 · DOI 10.3389/fimmu.2025.1696830