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TIL(肿瘤浸润淋巴细胞)扩增方案在癌症过继细胞治疗中的应用

英文原题:Tumor-infiltrating lymphocyte expansion protocols for adoptive cell therapy in cancer.

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Tumor-infiltrating lymphocyte expansion protocols for adoptive cell therapy in cancer.

PubMed 2025/11/17(内容时间) Cell Oncol (Dordr) Q1 · IF 5.6(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

TIL(肿瘤浸润淋巴细胞)(TILs)过继细胞治疗(ACT)已成为癌症免疫治疗中的一种创新策略,尤其是在实体瘤治疗中。本综述对当前TILs扩增方案进行了全面分析,重点关注旨在优化其性能、可行性和功能性的策略。经典的TILs扩增方案基于两步流程:快速预扩增阶段(Pre-REP),随后是快速扩增阶段(REP),其中使用高浓度的白细胞介素-2(IL-2)。近年来,该方案引入了多种改良,旨在提高其效率,包括使用IL-7、IL-15和IL-21等细胞因子的替代组合,以及用其他策略替代辐照饲养细胞或抗CD3抗体。

此外,新抗原特异性TILs的靶向、CAR-TILs的开发、人工智能的应用以及TILs的基因修饰等进展,均有助于拓展该疗法的适用性和疗效。Lifileucel的临床成功以及近期FDA的批准凸显了基于TILs疗法的转化潜力。

然而,重大挑战仍然存在,包括时间和生产成本。本综述探讨了正在进行的临床试验和联合治疗策略,例如免疫检查点抑制剂的使用。随着研究的进展,TILs扩增方案的优化对于改善临床结局和拓宽这种个性化免疫疗法在肿瘤学中的适用性至关重要。不适用。

展开英文摘要原文

Adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TILs) has emerged as an innovative strategy in cancer immunotherapy, especially in the treatment of solid tumors. This review provides a comprehensive analysis of current TILs expansion protocols, with a focus on strategies aimed at optimizing their performance, feasibility and functionality.

The classical TILs expansion protocol is based on a two-step process: a rapid pre-expansion phase (Pre-REP), followed by a rapid expansion phase (REP), in which high concentrations of interleukin-2 (IL-2) are used. In recent years, various modifications have been incorporated into the protocol with the aim of improving its efficiency, including the use of alternative combinations of cytokines such as IL-7, IL-15, and IL-21, as well as the replacement of irradiated feeder cells or anti-CD3 antibodies with other strategies.

Furthermore, advances such as the targeting of TILs specific to neoantigens, the development of CAR-TILs, the application of artificial intelligence, and the genetic modification of TILs have contributed to expanding both the applicability and efficacy of this therapy. The clinical success of Lifileucel with the recent FDA approval of underscore the translational potential of TILs-based therapies.

However, significant challenges remain, including time and production costs. This review examines ongoing clinical trials and combination therapeutic strategies, such as the use of immune checkpoint inhibitors. As research progresses, optimization of TILs expansion protocols will be critical to improving clinical outcomes and broadening the applicability of this personalized immunotherapy in oncology. Not applicable.

论文信息

作者
Tovar Manzano D、Subhi-Issa N、Pereiro-Rodríguez A、López Cade IG、Mateos González M、Fernández Arquero M、Pérez Segura P、Ujaldón Miró C
第一作者单位
Department of Clinical Immunology, Unidad de Inmunomonitorización del Cáncer y de Patologías Inmunomediadas (UICPI), Hospital Clínico San Carlos, IdISSC, Madrid, 28040, Spain.Spain
通讯作者单位
Department of Clinical Immunology, Unidad de Inmunomonitorización del Cáncer y de Patologías Inmunomediadas (UICPI), Hospital Clínico San Carlos, IdISSC, Madrid, 28040, Spain. mguzmanf@salud.madrid.org.Spain
文献类型
综述
期刊
Cellular oncology (Dordrecht, Netherlands)2025 Dec
原文标识
PubMed 41247618 · DOI 10.1007/s13402-025-01112-2