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However, the complex interplay between antigen transport, lymphatic drainage, and immune cell dynamics across organs remains poorly understood, limiting the rational design of vaccination strategies. Here, we present a multiscale compartmental Physiologically Based Pharmacokinetic\/Pharmacodynamic (PBPK\/PD) model of antigen vaccination that integrates systemic circulation, lymphatic connectivity, and immune cell activation at the whole\u2010body level. The model incorporates arterial, venous, and lymphatic flows, organ\u2010specific interstitium and lymph node (LN) networks, and a superficial skin network. The model reproduces spatiotemporal distributions of antigen and suppressive factors, APC activation, and nT priming across activation sites, including LNs and spleen. Our results show that the sensitivity of vaccination\u2010induced immunity is highly related to antigen and suppressive factor production by the tumor, and that early\u2010stage vaccination enhances immunity. Since the model is able to identify optimal vaccination administration over the course of tumor growth for each patient with certain levels of antigen and immunosuppressive factors, it can serve as the foundation for digital twins of patients to help inform anti\u2010cancer vaccination strategies.<\/jats:p>","DOI":"10.1002\/advs.78044","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:54:39Z","timestamp":1790823279000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimizing Cancer Vaccinations Using a Physiologically\u2010Based Pharmacokinetic\/Pharmacodynamic (PBPK\/PD) Model"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4648-7067","authenticated-orcid":false,"given":"Mohammad","family":"R. 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