免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor-infiltrating lymphocyte (TIL) therapy: Historical context, clinical applications, and future directions.
Tumor-infiltrating lymphocyte (TIL) therapy: Historical context, clinical applications, and future directions.
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在过去15年中,免疫治疗已成为癌症治疗的主要策略。TIL(肿瘤浸润淋巴细胞)治疗的研究已开展近四十年,并于2024年获得美国食品药品监督管理局首次批准,当时lifileucel被批准用于既往接受过治疗的转移性黑色素瘤患者。TIL治疗是一种基于细胞的免疫治疗形式,使用从肿瘤微环境中分离的自体T细胞,这些细胞经体外扩增后,在淋巴细胞清除性化疗和大剂量白介素-2之后回输,以介导肿瘤消退。当前数据表明,在一部分经过重度预治疗的晚期黑色素瘤患者中可获得持久缓解,早期临床研究提示其在其他免疫原性实体瘤中具有活性。在本综述中,总结了TIL治疗的历史发展、其当前临床应用、为优化产品组成和肿瘤微环境而出现的新策略,以及外科医生在TIL获取和递送中的关键作用。
In the past 15 years, immunotherapy has become a major strategy for cancer therapy. Tumor-infiltrating lymphocyte (TIL) therapy has been under investigation for nearly four decades and received its first Food and Drug Administration approval in 2024, when lifileucel was approved for patients with previously treated metastatic melanoma. TIL therapy is a form of cell-based immunotherapy that uses autologous T cells isolated from the tumor microenvironment, which are expanded ex vivo and reinfused to mediate tumor regression after lymphodepleting chemotherapy and high-dose interleukin-2.
Current data demonstrate durable responses in a subset of heavily pretreated patients with advanced melanoma, and early clinical studies suggest activity in other immunogenic solid tumors. In this review, the historical development of TIL therapy, its current clinical applications, emerging strategies to optimize product composition and the tumor microenvironment, and the critical role of surgeons in TIL procurement and delivery are summarized.
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