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CAR-T 治疗在实体瘤中的陷阱与策略及对脊索瘤治疗的启示

英文原题:Pitfalls and strategies of CAR-T therapy in solid tumors and implications for chordoma treatment.

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Pitfalls and strategies of CAR-T therapy in solid tumors and implications for chordoma treatment.

PubMed 2025/08/09(内容时间) Immunotherapy Q3 · IF 2.3(JCR 2025)

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中文摘要

近年来,CAR-T 细胞疗法已成为一种有前景的免疫治疗方法,在白血病、淋巴瘤等血液系统恶性肿瘤中显示出显著疗效。然而,其治疗实体瘤的效果仍有限,面临缓解率低、疗效持久性差和复发率高等挑战。实体瘤独特而复杂的免疫微环境具有致密的细胞外基质以及大量免疫抑制细胞和细胞因子,被认为是妨碍 CAR-T 细胞浸润、抗肿瘤活性和持续存在的主要因素,显著限制了该疗法的临床潜力。为应对这些挑战,研究者开发了多种策略以优化 CAR-T 细胞功能和适应性。脊索瘤是一种罕见且高度复杂的实体瘤,CAR-T 治疗面临多项难题,包括缺乏肿瘤特异性抗原、细胞外基质丰富,以及 TGF-β 等免疫抑制因子富集。本综述总结了增强 CAR-T 细胞治疗实体瘤的主要挑战及相应策略,并特别关注其治疗脊索瘤的潜在价值。

展开英文摘要原文

In recent years, CAR-T cell therapy has emerged as a promising immunotherapeutic approach, demonstrating remarkable therapeutic efficacy in hematologic malignancies such as leukemia and lymphoma.

However, its effectiveness in treating solid tumors remains limited, with challenges such as low response rates, poor therapeutic persistence, and high recurrence rates. The unique and complex immune microenvironment of solid tumors, characterized by a dense extracellular matrix, an abundance of immunosuppressive cells, and cytokines, is considered a major factor impeding CAR-T cell infiltration, antitumor activity, and persistence, significantly hindering the clinical potential of this therapy.

To address these challenges, various strategies have been developed to optimize CAR-T cell functionality and adaptability. As a rare and highly complex solid tumor, chordoma presents with several challenges for CAR-T cell therapy, including the lack of tumor-specific antigens, rich extracellular matrix, and enrichment of immunosuppressive factors such as TGF- .

This review summarizes the key challenges and corresponding strategies to enhance CAR-T cell therapy in solid tumors, with a particular focus on underlying its therapeutic potential for the treatment of chordoma.

论文信息

作者
Qi M、Cattaneo G、Camillo C、Quattrocchi E、Zhang L、Tejeda-Polanco E、Ferrone C、Chen Z
单位
Department of Orthopaedics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.United States
文献类型
综述
期刊
Immunotherapy2025 Jul
原文标识
PubMed 40782028 · DOI 10.1080/1750743X.2025.2536458