Amit Kumar, Luni Emdad, Swadesh K Das, Paul B Fisher
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引用次数: 0
Abstract
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.
采用嵌合抗原受体(CAR)技术的适应性细胞疗法通过采用先进的工程平台促进癌症免疫疗法,已成为主流疗法。CAR T 细胞在治疗血液恶性肿瘤方面已显示出显著疗效,但在实体瘤方面,这种疗法的价值仍无定论。实体瘤的免疫疗法受到多种障碍的制约,包括存在免疫抑制性肿瘤微环境(TME)、肿瘤贩运受限、免疫细胞浸润受抑制、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反应。尽管最近在 CAR T 细胞构建方面取得了进展,包括整合共刺激域和创建武装 CAR T 细胞,并在治疗某些实体瘤方面取得了可喜的成果,但仍有许多尚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,其他免疫细胞,如自然杀伤细胞和巨噬细胞,已被设计成具有吸引力的替代品,用于成功治疗实体瘤的癌症免疫疗法。CAR NK 细胞由于随时可用且毒性极低,在临床上具有显著优势。CAR 巨噬细胞(M)能够穿透实体瘤的 TME,因此具有相当大的治疗潜力。在这篇综述中,我们全面探讨了专为治疗实体瘤而设计的基于工程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的临床试验,这些临床试验正在研究 CAR T、CAR NK 和 CAR M 等改良免疫细胞的安全性和有效性,这些细胞能够特异性地靶向实体瘤,促进改善各种实体瘤患者的治疗效果。