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引用次数: 0
摘要
嵌合抗原受体(CAR)-T 是最有前途的现代癌症免疫疗法之一。近年来,该疗法在癌症治疗方面取得了令人瞩目的成果,并被美国食品及药物管理局批准用于液态肿瘤的治疗。在这种以细胞为基础的疗法中,免疫细胞(如 T 细胞和 NK 细胞)被设计为表达合成受体 CAR,以特异性识别和清除表达靶抗原的细胞。CAR 经过了不同世代的发展,旨在提高其生物活性,克服持久性低、效力有限、毒性危及生命以及对实体瘤活性低等局限性。本综述概述了不同世代的 CAR,从细胞毒性活性有限的第一代开始,直到最新的第五代或新一代,它们都是为了克服 CAR T 疗法的各种局限性而开发的。本文还讨论了目前正在进行的癌症和自身免疫性疾病临床试验,以及 CAR-T 细胞在癌症治疗中的局限性。
Chimeric antigen receptor (CAR)-T is one of the most promising modern cancer immunotherapies. In the recent years, impressive results have been obtained in the treatment of cancer which led to FDA approval for the treatment of liquid tumors. In this cell-based therapy, immune cells (e.g. T and NK cells) are engineered to express a synthetic receptor CAR to specifically recognize and eliminate cells expressing a target antigen. CAR has evolved through different generations aiming to boost its biological activity and overcome limitations such as low persistence, limited potency, life-threatening toxicity and inefficient activity against solid tumor. The present review provides an overview of the different CAR generations, starting from the 1st generation with limited cytotoxic activity until the latest generation, the 5th generation or new generation, developed to overcome various limitations of CAR T therapy. The current ongoing clinical trials in cancer and autoimmune diseases, and the limitation associated with CAR-T cells in cancer therapy, are also discussed.
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