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无同种异体反应性 CAR-VST 疗法:在病毒背景下长期控制肿瘤的一大进步

英文原题:Alloreactive-free CAR-VST therapy: a step forward in long-term tumor control in viral context.

查看英文原题

Alloreactive-free CAR-VST therapy: a step forward in long-term tumor control in viral context.

PubMed 2025/01/15(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

CAR-T 细胞疗法已经彻底改变了免疫治疗,但其使用多种策略的同种异体应用仍面临显著挑战,包括移植物抗宿主病和移植物排斥。近期利用病毒特异性 T 细胞生成 CAR-VST 的进展已显示出增强持久性和抗肿瘤疗效的潜力,使 CAR-VST 成为同种异体环境中传统 CAR-T 细胞的有前景替代方案。本综述全面概述了 CAR-VST 的发展,重点介绍了减轻免疫原性的策略,例如使用特化 TCR,以及改善针对宿主免疫反应的治疗持久性的方法。在本综述中,我们讨论了 CAR-VST 的生产方法,并探索了增强其功能性、激活特征、记忆持久性和抗耗竭能力的优化策略。重点放在其同时针对抗肿瘤和抗病毒反应的独特双重特异性,并深入审视了临床前和临床结局。

我们强调了这些进展如何促进 CAR-VST 在治疗环境中的疗效和持久性,为广泛的临床应用提供了新视角。通过聚焦使 CAR-VST 能够应对自体 CAR-T 细胞挑战的关键机制,本综述强调了其作为开发有效同种异体 CAR-T 疗法有前景策略的潜力。

展开英文摘要原文

CAR-T cell therapy has revolutionized immunotherapy but its allogeneic application, using various strategies, faces significant challenges including graft-versus-host disease and graft rejection. Recent advances using Virus Specific T cells to generate CAR-VST have demonstrated potential for enhanced persistence and antitumor efficacy, positioning CAR-VSTs as a promising alternative to conventional CAR-T cells in an allogeneic setting.

This review provides a comprehensive overview of CAR-VST development, emphasizing strategies to mitigate immunogenicity, such as using a specialized TCR, and approaches to improve therapeutic persistence against host immune responses.

In this review, we discuss the production methods of CAR-VSTs and explore optimization strategies to enhance their functionality, activation profiles, memory persistence, and exhaustion resistance. Emphasis is placed on their unique dual specificity for both antitumor and antiviral responses, along with an in-depth examination of preclinical and clinical outcomes.

We highlight how these advances contribute to the efficacy and durability of CAR-VSTs in therapeutic settings, offering new perspectives for broad clinical applications. By focusing on the key mechanisms that enable CAR-VSTs to address autologous CAR-T cell challenges, this review highlights their potential as a promising strategy for developing effective allogeneic CAR-T therapies.

论文信息

作者
Wang V、Savoldo B、Guimaraes JA、Dotti G、Reppel L、Bensoussan D
单位
Unité Mixte de Recherche (UMR) 7365 Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire, Cellulaire et Physiopathologie (IMoPA), Université de Lorraine, Nancy, France.France
文献类型
综述 · 非美国政府资助研究
期刊
Frontiers in immunology2024
原文标识
PubMed 39882248 · DOI 10.3389/fimmu.2024.1527648