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Here, this work reports the development of a biodegradable implant, designed for the localized co\u2010delivery of CD40 agonist and anti\u2013PD\u20101 antibodies, and evaluate its therapeutic effect in an aggressive KPC mouse model of PDAC. This localized approach significantly reduces tumor burden compared to controls and markedly attenuated systemic toxicities relative to conventional systemic administration. Immune profiling via transcriptomic analysis and flow cytometry revealed tumor microenvironment reprogramming, characterized by elevated dendritic cell activation (CD86\u207aCD11c\u207a), increased CD8\u207a T cell infiltration, and reduced expression of genes associated with myeloid\u2010derived suppressor cells. Histopathology confirms improved tolerability. These findings demonstrate that localized co\u2010delivery of CD40 and PD\u20101 immunotherapy via a biodegradable implant promotes anti\u2010tumor immunity while reducing systemic toxicity and immunotherapy\u2010associated complications. This strategy offers a promising alternative to systemic immunotherapy for PDAC and may help overcome the barriers of toxicity and immune resistance in this disease.<\/jats:p>","DOI":"10.1002\/adhm.202503780","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T09:28:32Z","timestamp":1762766912000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Localized Delivery of Anti\u2010CD40\/PD\u20101 Immunotherapy via a Polymeric Implant is Efficacious, Remodels the Tumor Immune Microenvironment and Improves Safety in a PDAC Mouse Model"],"prefix":"10.1002","volume":"15","author":[{"given":"Elahe","family":"Minaei","sequence":"first","affiliation":[{"name":"School of Science Faculty of Science Medicine and Health University of Wollongong Wollongong NSW 2522 Australia"},{"name":"Molecular Horizons University of Wollongong Wollongong NSW 2522 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