浙江大学顾臻团队取得一项新突破。他们研制了致敏肥大细胞用于靶向药物递送和增强癌症免疫治疗。相关论文于2025年12月9日发表在《细胞》杂志上。
研究人员设计了免疫球蛋白E （IgE）致敏肥大细胞（IgE- mcs），以实现抗原引导的溶瘤腺病毒主题（OVs）递送和局部免疫激活。通过利用肿瘤特异性抗原作为过敏原，IgE-MCs在抗原阳性肿瘤中积累，实现OV靶向递送和释放趋化因子和炎症介质，重塑肿瘤微环境。在几种小鼠模型中，包封OVs的IgE-MCs诱导小鼠抗癌免疫反应并抑制肿瘤生长。
值得注意的是，在人源化的人表皮生长因子受体-2 （HER2）阳性患者来源的异种移植物模型中，携带抗HER2 IgE并装载OVs的人MCs增加了肿瘤内T细胞反应并降低了肿瘤生长，这在临床相关环境中证明了可行性，并支持患者特异性IgE选择。总之，他们的研究强调了IgE-MCs作为癌症免疫治疗抗原特异性传递平台的转化前景。
研究人员表示，细胞介导的药物传递系统因其在癌症治疗中提高疗效的潜力而引起了极大的关注。
附：英文原文
Title: Sensitized mast cells for targeted drug delivery and augmented cancer immunotherapy
Author: Yan Xu, Xiaoge Zhang, Xiao Han, Hanwei Huang, Chaoyang Meng, Yinxian Yang, Tao Sheng, En Ren, Jiaqi Shi, Kaixin He, Dong Cen, Peng Zhao, Weijia Fang, Hongjun Li, Yuqi Zhang, Xiujun Cai, Funan Liu, Jicheng Yu, Zhen Gu
Issue&Volume: 2025-12-09
Abstract: Cell-mediated drug-delivery systems have garnered significant attention for their potential to boost therapeutic efficacy in cancer treatment. Here, we engineered immunoglobulin E (IgE)-sensitized mast cells (IgE-MCs) to achieve antigen-guided delivery of oncolytic adenoviruses (OVs) and local immune activation. By harnessing tumor-specific antigens as allergens, IgE-MCs accumulated at antigen-positive tumors, enabling targeted OV delivery and releasing chemokines and inflammatory mediators that remodeled the tumor microenvironment. IgE-MCs encapsulating OVs induced robust anticancer immune responses and inhibited tumor growth in several murine models. Of note, in a humanized human epidermal growth factor receptor-2 (HER2)-positive patient-derived xenograft model, human MCs armed with anti-HER2 IgE and loaded with OVs increased intratumoral T cell responses and reduced tumor growth, demonstrating feasibility in a clinically relevant setting and supporting patient-specific IgE selection. Together, our study highlights the translational promise of IgE-MCs as an antigen-specific delivery platform for cancer immunotherapy.
DOI: 10.1016/j.cell.2025.11.015
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01311-X