肿瘤浸润淋巴细胞(TIL)制剂制备质量管理专家共识

Expert Consensus on Quality Management of Tumor-Infiltrating Lymphocyte(TIL)Preparation

近年来,采用肿瘤浸润淋巴细胞(TIL)进行过继性T细胞疗法(ACT)的新型免疫治疗方式备受关注。TIL是从肿瘤组织中分离出的一种新型的抗肿瘤效应淋巴细胞,具有高效、特异、不良反应小等优点,临床应用潜在治疗价值巨大。国内外已有多家企业布局TIL疗法:2024年,美国FDA加速批准了LN-144,用于治疗PD-1耐药的晚期黑色素瘤患者;国内暂无TIL疗法的上市产品。鉴于TIL细胞的来源、类型、生产工艺等方面异质性较大,以及肿瘤组织的获取与运输要求、纯化TIL细胞获取方法、产品放行检测项目等有关TIL制剂生产安全性和质量方面的国家标准和行业标准均无统一规范,因此,制订针对性的TIL制剂制备标准对于全面保证TIL细胞制剂质量的安全性、有效性和可控性具有积极意义。为加强TIL制剂的质量控制,规范和指导TIL细胞制剂制备的质量管理,我院集合领域内众专家学者,参考国家免疫细胞治疗产品有关文件,结合TIL细胞特点,针对TIL制剂关键工艺步骤对质量控制要素和质量控制技术方法进行规定,特别编撰了《肿瘤浸润淋巴细胞(TIL)制剂制备质量管理专家共识》,以期为国家制定TIL制剂制备管理相关政策提供借鉴和参考。该共识明确了编制背景、TIL制剂生产术语、生产条件、质量控制要求、检测方法,重点阐述了肿瘤组织的采集和运输、TIL细胞的分离和纯化、TIL细胞的激活与扩增、TIL细胞制剂的放行等TIL制剂生产质量管理内容,适用于TIL制剂生产的质量控制。

In recent years,adoptive T cell therapy(ACT)with tumor-infiltrating lymphocyte(TIL)has received much attention.TIL is a new type of lymphocyte with anti-tumor effect which is isolated from tumor tissue,and has the advantages of high efficiency and speci-ficity,low side effects,and has great potential therapeutic value in clinical application.TIL therapy has been developed by several com-panies at home and abroad.LN-144 was approved by US FDA in 2024 for PD-1-resistant advanced melanoma patients,and there is no approved TIL therapy product in China yet.In view of the great heterogeneity in the source,type and production process of TIL cells,and there is no unified national and industry standards on the safety and quality of TIL preparations,such as the requirements of obtaining and transporting tumor tissues,the methods of obtaining purified TIL cells,and the items of product release and testing.Therefore,the estab-lishment of specific TIL preparation standards is of positive significance for ensuring the safety,effectiveness and controllability of TIL preparations.In order to strengthen the quality control of TIL preparation,standardize and guide the quality management of TIL prepara-tion,referring to the relevant documents on immunocyte therapy products and combining the characteristics of TIL cells,the“Expert Con-sensus on Quality Management of Tumor-Infiltrating Lymphocyte(TIL)Preparation”was compiled,in which the quality control elements and quality control technical methods were described according to the key process steps of TIL preparation,so as to provide reference for the formulation of relavant policies on TIL preparation management in China.The background,terminology,production conditions,qual-ity control requirements and testing methods of TIL preparation were defined in this consensus,and the content of production quality man-agement of TIL preparations,such as collection and transportation of tumor tissues,isolation and purification of TIL cells,activation and expansion of TIL cells,release of TIL preparations were emphasized.This consensus is suitable for the quality control of TIL preparations.