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Here, we develop engineered macrophages by conjugating oncolytic adenovirus (OA)\u2010loaded zeolitic imidazolate framework\u20108 (ZIF\u20108) onto macrophage surfaces via bioorthogonal chemistry (ZIFOA\u2010M). This platform leverages localized viral delivery to selectively downregulate \u201cdon't eat me\u201d signals (CD47 and CD24) on tumor cells, thereby restoring macrophage phagocytic capacity. Moreover, viral replication within tumors induces immunogenic cell death, releasing major damage\u2010associated molecular patterns (DAMPs) that sustain M1\u2010type polarization and promote durable antitumor immunity. ZIFOA\u2010M also enhances tumor antigen presentation, eliciting robust tumor\u2010specific T cell responses. Our strategy integrates phagocytosis restoration, microenvironment remodeling, and adaptive immune activation in a single, localized platform. ZIFOA\u2010M offers a complementary and translatable approach to overcome key barriers in macrophage\u2010based cancer immunotherapy.<\/jats:p>","DOI":"10.1002\/advs.75406","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T10:51:38Z","timestamp":1776682298000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Engineering Oncolytic Virus\u2010Armed Macrophages for Enhanced Cancer Immunotherapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Jilong","family":"Wang","sequence":"first","affiliation":[{"name":"Joint Centre of Translational Medicine The First Affiliated Hospital of Wenzhou Medical University Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Joint Centre of Translational Medicine Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou Zhejiang 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