Department of Oncology, Lausanne University Hospital, and Ludwig Institute for Cancer Research, University of Lausanne, 1066, Lausanne, Switzerland.
Drug Saf. 2019 Feb;42(2):315-334. doi: 10.1007/s40264-018-0779-3.
Adoptive T cell therapy (ACT) is a safe and effective personalized cancer immunotherapy that can comprise naturally occurring ex vivo expanded cells (e.g., tumor-infiltrating lymphocytes [TIL]) or T cells genetically engineered to confer antigen specificity (T-cell receptor [TCR] or chimeric antigen receptor [CAR] engineered T cells) to mediate cancer rejection. In recent years, some ACTs have produced unprecedented breakthrough responses: TIL therapy has moved from melanoma to solid tumor applications, TCR-engineered cells are developed for hematologic and solid tumors, and CAR-engineered T cells have received Food and Drug Administration (FDA) approval for the treatment of patients with certain B-cell malignancies. Although results are encouraging, to date, only a small percentage of patients with advanced malignancies can benefit from ACT. Besides ACT availability and accessibility, treatment-related toxicities represent a major hurdle in the widespread implementation of this therapeutic modality. The large variety of observed toxicities is caused by the infused cell product or as side effects of accompanying medication and chemotherapy. Toxicities can occur immediately or can be delayed. In order to render those highly promising therapeutic approaches safe enough for a wider pool of patients outside of clinical trials, an international consensus for toxicity management needs to be established.
过继性 T 细胞疗法（ACT）是一种安全有效的个性化癌症免疫疗法，它可以包括天然存在的体外扩增细胞（例如，肿瘤浸润淋巴细胞[TIL]）或经过基因工程改造以赋予抗原特异性的 T 细胞（T 细胞受体[TCR]或嵌合抗原受体 [CAR] 工程 T 细胞），以介导癌症排斥。近年来，一些 ACT 产生了前所未有的突破性反应：TIL 疗法已从黑色素瘤扩展到实体瘤应用，TCR 工程细胞正在开发用于血液系统和实体瘤，CAR 工程 T 细胞已获得美国食品和药物管理局（FDA）批准用于治疗某些 B 细胞恶性肿瘤的患者。尽管结果令人鼓舞，但迄今为止，只有少数晚期恶性肿瘤患者可以从 ACT 中受益。除了 ACT 的可用性和可及性外，与治疗相关的毒性是广泛实施这种治疗方式的主要障碍。观察到的大量毒性是由输注的细胞产品或伴随药物和化疗的副作用引起的。毒性可能立即发生，也可能延迟发生。为了使这些极具前景的治疗方法对临床试验之外更广泛的患者群体足够安全，需要建立一种国际共识来管理毒性。
