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Sensitized mast cells for targeted drug delivery and augmented cancer immunotherapy

Yan Xu1, Xiaoge Zhang1, Xiao Han2

  • 1State Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang Provincial Key Laboratory for Advanced Drug Delivery Systems, School of Pharmacy, Zhejiang University, Hangzhou 310058, Zhejiang, China; Liangzhu Laboratory, Zhejiang University, Hangzhou 311121, Zhejiang, China.

Cell
|December 10, 2025
PubMed

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.

Keywords:
cancer immunotherapycell therapycell-drug conjugatedrug deliverymast cellsoncolytic adenoviruses

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