Sakamoto Kenichi, Yagyu Shigeki
Department of Pediatrics, Shinshu University School of Medicine.
Shinshu University Innovative Research & Liaison Organization.
Rinsho Ketsueki. 2024;65(7):652-661. doi: 10.11406/rinketsu.65.652.
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigm for refractory/relapsed (R/R) hematologic malignancies, with six products approved for B-cell tumors and multiple myeloma as of the end of 2023. However, adoptive cell therapy (ACT) for solid tumors is hindered by critical challenges in multiple areas, including (1) lack of appropriate tumor-specific antigens, (2) inefficient T-cell trafficking and infiltration into the tumor microenvironment, and (3) immunosuppressive signals within the tumor milieu that induce T-cell dysfunction. This review examines the existing clinical trial data on ACT for solid tumors to elucidate the current landscape of ACT development for solid tumors. It also outlines the trajectory of ACT for solid tumors and integrative approaches to overcoming the complex tumor microenvironment.
嵌合抗原受体(CAR)T细胞疗法彻底改变了难治性/复发性(R/R)血液系统恶性肿瘤的治疗模式,截至2023年底,已有六种产品获批用于治疗B细胞肿瘤和多发性骨髓瘤。然而,实体瘤的过继性细胞疗法(ACT)在多个领域面临严峻挑战,包括(1)缺乏合适的肿瘤特异性抗原,(2)T细胞向肿瘤微环境的转运和浸润效率低下,以及(3)肿瘤微环境中诱导T细胞功能障碍的免疫抑制信号。本综述审视了关于实体瘤ACT的现有临床试验数据,以阐明实体瘤ACT的当前发展态势。它还概述了实体瘤ACT的发展轨迹以及克服复杂肿瘤微环境的综合方法。