丹娜-法伯癌症研究所Kai W. Wucherpfennig团队取得一项新突破。他们的研究开发出了临床试验中单一溶瘤病毒治疗后对胶质母细胞瘤的持续T细胞活化和细胞毒性。该项研究成果发表在2026年2月11日出版的《细胞》上。
该团队提供了原位证据，证明在单次治疗后的较晚时间点，T细胞介导的细胞毒性对肿瘤细胞持续存在，T细胞深度持续浸润到肿瘤区域。劈裂的caspase-3+肿瘤细胞和颗粒酶B+T细胞之间的距离越短，治疗后的无进展生存期越长。预先存在的肿瘤浸润性T细胞在治疗后局部扩增，与更长的患者总体生存期相关。具有早期激活程序的T细胞与肿瘤细胞密切相互作用，并在治疗后强烈富集。病毒残余物局限于坏死区域，而T细胞则深入浸润到活的肿瘤区域。这些数据表明，单一溶瘤病毒治疗可以扩大已有的T细胞克隆，并触发持久性T细胞介导的针对GBM的免疫。
据介绍，最近的一项首次人体临床试验表明，rQNestin34.5v.2溶瘤病毒治疗后胶质母细胞瘤（GBM）患者的存活率与免疫激活特征有关。本研究已在ClinicalTrials.gov注册（NCT03152318）。
附：英文原文
Title: Persistent T cell activation and cytotoxicity against glioblastoma following single oncolytic virus treatment in a clinical trial
Author: Maxime Meylan, Ye Tian, Lijian Wu, Alexander L. Ling, Daniel Kovarsky, Graham L. Barlow, Linh D. Nguyen, Jason Pyrdol, Sascha Marx, Lucas Westphal, Julius Michel, L. Nicolas Gonzalez Castro, Sydney Dumont, Andres Santos, Itay Tirosh, Mario L. Suvà, E. Antonio Chiocca, Kai W. Wucherpfennig
Issue&Volume: 2026-02-11
Abstract: A recent first-in-human clinical trial demonstrated that survival in glioblastoma (GBM) patients following rQNestin34.5v.2 oncolytic virus treatment was associated with immune activation signatures. This study was registered at ClinicalTrials.gov (NCT03152318). Here, we provide in situ evidence of ongoing T cell-mediated cytotoxicity against tumor cells at late time points following single treatment, with deep and persistent T cell infiltration into tumor regions. Shorter distances between cleaved caspase-3+ tumor cells and granzyme B+ T cells were associated with longer progression-free survival following treatment. Pre-existing tumor-infiltrating T cells expanded locally upon treatment, correlating with longer overall patient survival. T cells with an early activation program closely interacted with tumor cells and were strongly enriched upon treatment. Viral remnants were restricted to necrotic regions, while T cells infiltrated deeply into live tumor regions. These data demonstrate that single oncolytic virus treatment can expand pre-existing T cell clones and trigger persistent T cell-mediated immunity against GBM.
DOI: 10.1016/j.cell.2025.12.055
Source:https://www.cell.com/cell/abstract/S0092-8674(25)01504-1