Liu Shiyu, Jiang Weibo, Sheng Jiyao, Wang Lixuan, Cui Mengying
Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China.
Orthopedic Medical Center, The Second Hospital of Jilin University, Changchun, Jilin, China.
Front Immunol. 2025 Aug 1;16:1603792. doi: 10.3389/fimmu.2025.1603792. eCollection 2025.
Adoptive cell therapy (ACT) is a therapeutic approach that involves the isolation, modification, and expansion of immune cells , followed by their reinfusion into the patient to enhance anti-tumor immune responses. Various forms of ACT have demonstrated promising clinical outcomes across multiple types of cancer. For example, chimeric antigen receptor (CAR)-T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, and T-cell receptor-engineered T cell (TCR-T) therapy have received approval from the US Food and Drug Administration. However, the clinical application of ACT remains constrained by limited efficacy and potentially life-threatening toxicities. Diminished efficacy may result from an immunosuppressive tumor microenvironment, poor trafficking and infiltration, exhaustion of infused cells, tumor heterogeneity, and antigen escape. To address these challenges, combination strategies have been developed with the goals of enhancing efficacy and managing adverse effects. Conventional treatments and non-ACT forms of immunotherapy have been incorporated into these combination approaches. Biomarkers play an essential role in optimizing ACT strategies and addressing associated complexities. They can aid in candidate selection, assess the quality of ACT products, monitor long-term therapeutic efficacy, manage toxicity, and guide combination regimens. This review briefly outlines six ACT modalities and their common limitations, summarizes current combination strategies, explores potential future regimens, and offers an overview of biomarkers relevant to ACT. These insights provide valuable guidance for the development and clinical implementation of more effective ACT-based therapies, ultimately aiming to improve patient outcomes.
过继性细胞疗法（ACT）是一种治疗方法，涉及免疫细胞的分离、改造和扩增，随后将其重新注入患者体内以增强抗肿瘤免疫反应。各种形式的ACT已在多种癌症类型中显示出有前景的临床结果。例如，嵌合抗原受体（CAR）-T细胞疗法、肿瘤浸润淋巴细胞（TIL）疗法和T细胞受体工程化T细胞（TCR-T）疗法已获得美国食品药品监督管理局的批准。然而，ACT的临床应用仍然受到疗效有限和潜在危及生命的毒性的限制。疗效降低可能是由于免疫抑制性肿瘤微环境、较差的转运和浸润、注入细胞的耗竭、肿瘤异质性以及抗原逃逸。为应对这些挑战，已开发出联合策略，目标是提高疗效并管理不良反应。传统治疗和非ACT形式的免疫疗法已被纳入这些联合方法中。生物标志物在优化ACT策略和解决相关复杂性方面发挥着重要作用。它们可有助于候选者选择、评估ACT产品质量、监测长期治疗疗效、管理毒性并指导联合治疗方案。本综述简要概述了六种ACT模式及其常见局限性，总结了当前的联合策略，探索了潜在的未来治疗方案，并概述了与ACT相关的生物标志物。这些见解为开发和临床实施更有效的基于ACT的疗法提供了有价值的指导，最终目标是改善患者预后。
