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.
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.
Adv Cancer Res. 2024;164:111-190. doi: 10.1016/bs.acr.2024.05.004. Epub 2024 May 31.
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.
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疗法，已成为主流。CAR T 细胞在治疗血液恶性肿瘤方面显示出显著的疗效；然而，这种疗法在实体瘤中的价值仍不确定。实体瘤的免疫疗法受到多种障碍的限制，包括存在免疫抑制性肿瘤微环境 (TME)、有限的肿瘤转移、抑制免疫细胞浸润、缺乏肿瘤特异性抗原以及与这些疗法相关的脱靶毒性和不良事件。尽管最近在 CAR T 细胞构建方面取得了进展，包括共刺激结构域的整合和武装 CAR T 细胞的创建，并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。为了克服有效 CAR T 细胞疗法的这些障碍，已经对其他免疫细胞（如自然杀伤细胞和巨噬细胞）进行了工程改造，以作为成功治疗实体瘤的癌症免疫疗法的有吸引力的替代方案。CAR NK 细胞由于其易得性和低毒性而具有显著的临床优势。CAR 巨噬细胞 (M) 细胞由于其能够穿透实体瘤的 TME，因此具有巨大的治疗潜力。在这篇综述中，我们全面检查了专门用于治疗实体瘤的基于工程化免疫细胞的癌症免疫疗法的最新进展和前景。此外，我们还简要概述了目前正在检查修饰后的免疫细胞（如 CAR T、CAR NK 和 CAR M）在特异性靶向实体瘤和促进不同实体癌患者治疗效果改善方面的安全性和有效性的临床试验。
