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However, their efficacy has often been hindered by weak and slow immune responses. Here, the authors introduce an immunization strategy employing senescent erythrocytes to facilitate the accumulation of immunomodulatory zinc\u2010Alum\/ovalbumin (ZAlum\/OVA) nanovaccines within both the spleen and solid tumors by temporarily saturating liver macrophages. This approach sets the stage for boosted cancer metalloimmunotherapy through a cascade immune activation. The accumulation of ZAlum\/OVA nanovaccines in the spleen substantially enhances autophagy\u2010dependent antigen presentation in dendritic cells, rapidly initiating OVA\u2010specific T\u2010cell responses against solid tumors. Concurrently, ZAlum\/OVA nanovaccines accumulated in the tumor microenvironment trigger immunogenic cell death, leading to the induction of individualized tumor\u2010associated antigen\u2010specific T cell responses and increased T cell infiltration. This erythrocyte\u2010assisted cascade immune activation using ZAlum\/OVA nanovaccines results in rapid and robust antitumor immunity induction, holding great potential for clinical cancer metalloimmunotherapy.<\/jats:p>","DOI":"10.1002\/advs.202307389","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T12:06:38Z","timestamp":1702037198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["An Immunomodulatory Zinc\u2010Alum\/Ovalbumin Nanovaccine Boosts Cancer Metalloimmunotherapy Through Erythrocyte\u2010Assisted Cascade Immune Activation"],"prefix":"10.1002","volume":"11","author":[{"given":"Jing","family":"Zhao","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutics Hangzhou Institute of Innovative Medicine College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 P. R. 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