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The efficacy of pre\u2010existing antiviral immunity in tumor treatment is limited by the absence of corresponding targets. This study develops a novel platform of antigen\u2010targeted inserted nanomicelles, preS1 (an antigen of hepatitis B virus)\u2010pHLIP nanomicelles, in which tumor\u2010targeting nanomicelles release antigens that label tumor tissue for pre\u2010existing immunity\u2010mediated lysis in situ. In animal models of head and neck cancers, including head and neck squamous cell carcinoma and anaplastic thyroid cancer, preS1\u2010pHLIP nanomicelles effectively inhibited tumor growth, recurrence, and metastasis in animals pre\u2010immunized with preS1. This therapeutic effect is associated with an increase in the proportion of preS1\u2010specific B cells and activated tumor\u2010specific T cells within the tumor microenvironment. Overall, this work has engineered a nanomicelle that can disguise tumor cells as viruses and achieve tumor killing through the pre\u2010existing antiviral immune response. This strategy presents a novel approach for treating tumors with ambiguous therapeutic target profiles.<\/jats:p>","DOI":"10.1002\/advs.202410629","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T03:15:47Z","timestamp":1742181347000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antigen\u2010Targeting Inserted Nanomicelles Guide Pre\u2010Existing Immunity to Kill Head and Neck Cancer"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4460-1743","authenticated-orcid":false,"given":"Lizhuo","family":"Zhang","sequence":"first","affiliation":[{"name":"Otolaryngology &amp; Head and Neck Center Cancer Center Department of Head and Neck Surgery Zhejiang Provincial People's Hospital (Affiliated People's Hospital) Hangzhou Medical College  Hangzhou 310014 China"},{"name":"Zhejiang Provincial Clinical Research Center for Head &amp; Neck Cancer  Hangzhou 310014 China"},{"name":"Zhejiang Key Laboratory of Precision Medicine Research on Head &amp; 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Peking Union Medical College  Beijing 100193 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiefeng","family":"Jin","sequence":"additional","affiliation":[{"name":"Cancer Centre Faculty of Health Sciences University of Macau  Macau SAR 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaofeng","family":"Hu","sequence":"additional","affiliation":[{"name":"Zhejiang Cancer Hospital  Hangzhou 310005 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Tan","sequence":"additional","affiliation":[{"name":"Otolaryngology &amp; Head and Neck Center Cancer Center Department of Head and Neck Surgery Zhejiang Provincial People's Hospital (Affiliated People's Hospital) Hangzhou Medical College  Hangzhou 310014 China"},{"name":"Zhejiang Provincial Clinical Research Center for Head &amp; Neck Cancer  Hangzhou 310014 China"},{"name":"Zhejiang Key Laboratory of Precision Medicine Research on Head &amp; Neck Cancer  Hangzhou 310014 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiafeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Otolaryngology &amp; 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