Vita-Salute San Raffaele University, Milan, Italy.
Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Front Immunol. 2020 Sep 3;11:1689. doi: 10.3389/fimmu.2020.01689. eCollection 2020.
Adoptive T cell therapy (ACT) is a rapidly evolving therapeutic approach designed to harness T cell specificity and function to fight diseases. Based on the evidence that T lymphocytes can mediate a potent anti-tumor response, initially ACT solely relied on the isolation, expansion, and infusion of tumor-infiltrating or circulating tumor-specific T cells. Although effective in a subset of cases, in the first ACT clinical trials several patients experienced disease progression, in some cases after temporary disease control. This evidence prompted researchers to improve ACT products by taking advantage of the continuously evolving gene engineering field and by improving manufacturing protocols, to enable the generation of effective and long-term persisting tumor-specific T cell products. Despite recent advances, several challenges, including prioritization of antigen targets, identification, and optimization of tumor-specific T cell receptors, in the development of tools enabling T cells to counteract the immunosuppressive tumor microenvironment, still need to be faced. This review aims at summarizing the major achievements, hurdles and possible solutions designed to improve the ACT efficacy and safety profile in the context of liquid and solid tumors.
过继性 T 细胞疗法（ACT）是一种快速发展的治疗方法，旨在利用 T 细胞的特异性和功能来对抗疾病。基于 T 淋巴细胞可以介导强大的抗肿瘤反应的证据，最初的 ACT 仅依赖于肿瘤浸润或循环肿瘤特异性 T 细胞的分离、扩增和输注。尽管在一些情况下有效，但在第一批 ACT 临床试验中，一些患者经历了疾病进展，在某些情况下是在暂时控制疾病后。这一证据促使研究人员利用不断发展的基因工程领域和改进制造方案来改进 ACT 产品，以生成有效和长期持续存在的肿瘤特异性 T 细胞产品。尽管最近取得了一些进展，但仍需要解决一些挑战，包括抗原靶点的优先级、肿瘤特异性 T 细胞受体的鉴定和优化，以及开发使 T 细胞能够对抗免疫抑制肿瘤微环境的工具。这篇综述旨在总结为提高液体和实体肿瘤中 ACT 的疗效和安全性而设计的主要成就、障碍和可能的解决方案。
