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实体瘤免疫治疗的最新进展

英文原题:Recent advances and progress in immunotherapy of solid cancers.

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Recent advances and progress in immunotherapy of solid cancers.

PubMed 2024/05/31(内容时间) Adv Cancer Res

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中文摘要

利用嵌合抗原受体(CAR)技术的过继细胞疗法通过采用先进的工程平台促进癌症免疫治疗已成为主流。CAR-T 细胞在血液系统恶性肿瘤的治疗中显示出显著疗效;然而,该疗法在实体瘤中的价值仍无定论。实体瘤的免疫治疗受到多种障碍的制约,包括免疫抑制性肿瘤微环境(TME)的存在、有限的肿瘤迁移、受抑制的免疫细胞浸润、肿瘤特异性抗原的缺失,以及脱靶毒性和与这些疗法相关的不良事件。尽管CAR-T 细胞构建方面取得了最新进展,包括整合共刺激结构域和创建装甲CAR-T 细胞,在一些实体瘤的治疗中取得了有希望的结果,但仍有许多未解决的障碍需要克服。为了克服这些阻碍有效CAR-T 细胞疗法的障碍,其他免疫细胞,如NK 细胞和巨噬细胞,已被工程化改造,作为成功实现实体瘤癌症免疫治疗的有吸引力的替代方案。CAR NK细胞因其易于获取和毒性极小,展现出显著的临床优势。CAR巨噬细胞(M)因其能够穿透实体瘤的TME而具有相当大的治疗潜力。在这篇综述中,我们全面审视了专门为治疗实体瘤而设计的基于工程化免疫细胞的癌症免疫治疗的最新进展和前景。

此外,我们简要概述了当前正在进行的临床试验,这些试验旨在检验修饰免疫细胞(如CAR-T、CAR NK和CAR M)在特异性靶向实体瘤并促进多种实体癌患者获得更好治疗结果方面的安全性和有效性。

展开英文摘要原文

Adoptive cell therapy using chimeric antigen receptor (CAR) technology has become mainstream by employing advanced engineering platforms to promote cancer immunotherapy. CAR T cells have shown remarkable efficacy in the treatment of hematological malignancies; however, the value of this therapy remains inconclusive in the context of solid tumors. Immunotherapy of solid tumors is restrained by several obstacles including the presence of an immunosuppressive tumor microenvironment (TME), limited tumor trafficking, inhibited immune cell infiltration, absence of tumor-specific antigens, and off-target toxicity and adverse events associated with these therapies.

Despite recent advances in CAR T cell construction, including the integration of co-stimulatory domains and the creation of armed CAR T cells, with promising outcomes in the treatment of some solid tumors, there are still many unresolved obstacles that need to be overcome. To surmount these impediments to effective CAR T cell therapies, other immune cells, such as natural killer cells and macrophages, have been engineered to serve as appealing alternatives for successful cancer immunotherapy of solid tumors.

CAR NK cells demonstrate significant clinical advantages due to their ready availability and minimal toxicity. CAR macrophage (M) cells provide considerable therapeutic potential due to their ability to penetrate the TME of solid tumors. In this review, we comprehensively examine the latest developments and prospects of engineered immune cell-based cancer immunotherapies specifically designed for treating solid tumors.

In addition, we provide a concise overview of current clinical trials that are examining the safety and effectiveness of modified immune cells, such as CAR T, CAR NK, and CAR M, in their ability to specifically target solid tumors and promote improved therapeutic outcomes in patients with diverse solid cancers.

论文信息

作者
Kumar A、Emdad L、Das SK、Fisher PB
第一作者单位
Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States. Electronic address: amit.kumar@vcuhealth.org.United States
通讯作者单位
Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Massey Comprehensive Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States. Electronic address: paul.fisher@vcuhealth.org.United States
文献类型
综述 · 非美国政府资助研究 · 美国 NIH 资助研究
期刊
Advances in cancer research2024
原文标识
PubMed 39306365 · DOI 10.1016/bs.acr.2024.05.004