复旦大学步文博团队开发出用于肿瘤免疫治疗的离子增强溶瘤病毒样纳米颗粒。相关研究成果于2022年9月18日发表于国际一流学术期刊《德国应用化学》。

T淋巴细胞（T细胞）对肿瘤免疫治疗至关重要。然而，激活的T细胞数量不足，极大地限制了肿瘤免疫治疗的效果。

该文中，研究人员提出了一种模拟溶瘤病毒策略，以增强肿瘤治疗中T细胞的聚集和激活。研究人员构建了一个类似溶瘤病毒的纳米平台(PolyIC@ZIF-8)在酸性肿瘤环境中降解，释放PolyIC和Zn²⁺。释放的PolyIC表现出一种溶瘤病毒样功能，通过肿瘤抗原依赖的方式诱导肿瘤细胞凋亡并促进T细胞聚集和激活。

更重要的是，释放的Zn²⁺不仅通过诱导CXCL9/10/11表达来增强T细胞聚集，而且通过诱导ZAP-70通过肿瘤抗原非依赖性方式磷酸化来促进T细胞活化以增加干扰素-γ（INF-γ）的表达。这种Zn²⁺增强的溶瘤病毒模拟策略为肿瘤免疫治疗提供了一种新的途径。

附：英文原文

Title: An Ion-Enhanced Oncolytic Virus-Like Nanoparticle for Tumor Immunotherapy

Author: Fan Wu, Yanli Li, Yun Meng, Xuechao Cai, Jieyun Shi, Jinjin Li, Yang Chen, Li Zhang, Xianfu Meng, Huiyan Li, Xingwu Jiang, Zhenxiao Fu, Yelin Wu, Wenbo Bu

Issue&Volume: 2022-09-18

Abstract: T lymphocytes (T cells) are essential for tumor immunotherapy. However,  the  insufficient number of activated T cells  greatly limits the efficacy of tumor immunotherapy.  Herein, we proposed an  oncolytic virus-mimicking strategy to enhance T cell recruitment and activation for tumor treatment. We constructed an  oncolytic virus-like  nanoplatform (PolyIC@ZIF-8)  that was degraded in the acidic tumor environment to  release PolyIC and  Zn2  +. The released PolyIC exhibited an  oncolytic virus-like function that induced tumor cell apoptosis and promoted T cell  recruitment  and activation through a tumor antigen-dependent manner. More importantly,  the released  Zn2+  not only enhanced T cell recruitment by inducing CXCL9/10/11 expression but also promoted T cell activation to increase interferon-γ (INF-γ) expression by i  nducing the phosphorylation of ZAP-70  via a tumor antigen-independent manner.  This Zn2+-enhanced  oncolytic  virus-mimicking strategy provides a new approach for tumor  immunotherapy  .

DOI: 10.1002/anie.202210487

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202210487