Chen Ruqin, Johnson Jeffrey, Rezazadeh Ali, Dudek Arkadiusz Z
Department of Medicine, Mayo Clinic, Jacksonville, Florida, USA.
Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.
BMJ Oncol. 2025 Aug 4;4(1):e000566. doi: 10.1136/bmjonc-2024-000566. eCollection 2025.
Tumour-infiltrating lymphocyte (TIL) therapy has emerged as a promising adoptive cell transfer strategy for solid tumours. The recent accelerated approval of lifileucel by the Food and Drug Administration marks a significant milestone in the clinical application of TIL therapy. This review comprehensively examines the historical development, biology, clinical efficacy, safety and limitations of TIL therapy. We explore advancements in TIL manufacturing, including novel culture techniques, genetic modifications and automation, to enhance scalability and effectiveness. Despite promising results, TIL therapy faces challenges such as high-dose interleukin-2 toxicity, complex manufacturing processes and immune evasion mechanisms. Emerging strategies, including checkpoint inhibitor combinations, engineered TIL constructs and metabolic reprogramming, aim to improve TIL therapeutic efficacy. This review provides insights into the evolving landscape of TIL therapy and its potential to enhance current cancer immunotherapy.
肿瘤浸润淋巴细胞（TIL）疗法已成为一种针对实体瘤颇具前景的过继性细胞转移策略。美国食品药品监督管理局最近加速批准了利夫鲁赛尔，这标志着TIL疗法临床应用中的一个重要里程碑。本综述全面审视了TIL疗法的历史发展、生物学特性、临床疗效、安全性及局限性。我们探讨了TIL生产方面的进展，包括新型培养技术、基因改造和自动化，以提高可扩展性和有效性。尽管取得了令人鼓舞的结果，但TIL疗法面临着诸如高剂量白细胞介素-2毒性、复杂的生产过程和免疫逃逸机制等挑战。包括检查点抑制剂联合使用、工程化TIL构建体和代谢重编程在内的新兴策略旨在提高TIL的治疗效果。本综述深入探讨了TIL疗法不断演变的格局及其增强当前癌症免疫疗法的潜力。
