在许多成年实体瘤中，正在研究用于过继性细胞治疗的肿瘤浸润淋巴细胞（TIL）的扩增。骨髓浸润淋巴细胞（MIL）已在临床前证明具有抗肿瘤反应活性。在儿科实体瘤组织学中尚未有 TIL/MIL 成功扩增的报道。本研究的目的是证明从儿科实体瘤中成功扩增 TIL，以转化为过继细胞疗法 (ACT) 治疗策略。对接受标准治疗的儿科患者实体瘤进行了 TIL/MIL 扩增的前瞻性研究。护理程序。 TIL/MIL 扩增是在高剂量白细胞介素 2 存在的情况下进行的。为了证明 TIL 治疗的临床相关细胞剂量的全面扩增，在初始 TIL 培养后，对选定的患者进行了快速扩增方案。通过流式细胞术分析扩增样本的表型并通过干扰素-γ释放测定分析抗肿瘤反应性。获得18个肿瘤样本。 14/18 个样本 (77.7%) 成功生成了初始 TIL 培养物。初始培养物产生中位数 5.52 × 107（范围：2.5 × 106-3.23 × 108）个细胞，其中 46.9% 表达 CD3 表型 (46.9%)。 8 个样本经历了快速扩增，显示中位扩增量为 458 倍，CD3 表型为 98%。最初的 MIL 培养物成功地从五个样品中产生，主要是 CD3 表型 (45.2%)。仅提供了 7 个 TIL 样本的足够肿瘤组织来测试反应性；没有一个表现出对自体肿瘤的反应。儿童实体瘤的 TIL 和 MIL 扩增是成功的，包括全面的扩增过程。该数据支持在儿科人群中转化为 ACT-TIL 治疗策略，因此计划对儿科高危实体瘤进行 ACT-TIL 的 I 期试验。版权所有 © 2024 国际细胞学会

The expansion of tumor-infiltrating lymphocytes (TIL) for adoptive cellular therapy is under investigation in many solid tumors of adulthood. Marrow-infiltrating lymphocytes (MIL) have demonstrated antitumor reactivity preclinically. Successful expansion of TIL/MIL has not been reported across pediatric solid tumor histologies. The objective of this study was to demonstrate successful expansion of TIL from pediatric solid tumors for translation in an adoptive cell therapy (ACT) treatment strategy.A prospective study of TIL/MIL expansion was performed on solid tumors of pediatric patients undergoing standard-of-care procedures. TIL/MIL expansions were performed in the presence of high-dose interleukin 2. To demonstrate a full-scale expansion to clinically-relevant cell doses for TIL therapy, initial TIL culture was followed by a rapid expansion protocol for select patients. Expanded specimens were analyzed for phenotype by flow cytometry and for anti-tumor reactivity by the interferon-gamma release assay.Eighteen tumor samples were obtained. Initial TIL cultures were successfully generated from 14/18 samples (77.7%). A median of 5.52 × 107 (range: 2.5 × 106-3.23 × 108) cells were produced from initial cultures, with 46.9% expressing a CD3 phenotype (46.9%). Eight samples underwent rapid expansion, demonstrating a median 458-fold expansion and a CD3 phenotype of 98%. Initial MIL cultures were successfully generated from five samples, with a predominantly CD3 phenotype (45.2%). Sufficient tumor tissue was only available for seven TIL samples to be tested for reactivity; none demonstrated responsiveness to autologous tumor.TIL and MIL expansion from pediatric solid tumors was successful, including the full-scale expansion process. This data supports translation to an ACT-TIL treatment strategy in the pediatric population and thus a Phase I trial of ACT-TIL in pediatric high-risk solid tumors is planned.Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.