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To overcome this resistance, we evaluated an oral WT1\u2010targeted cancer vaccine using a recombinant Bifidobacterium longum strain (\n                    <jats:italic>B. longum<\/jats:italic>\n                    420) engineered to display a partial WT1 antigen. Oral immunization with\n                    <jats:italic>B. longum<\/jats:italic>\n                    420 activated WT1\u2010associated cellular immunity, increasing IL\u201012\u2013producing CD45\n                    <jats:sup>+<\/jats:sup>\n                    cells and Th1\/cytotoxic cytokine\u2010producing T cells, and enhancing splenocyte cytotoxic activity against Pan02 cells. In a syngeneic Pan02 tumor model, the combination of\n                    <jats:italic>B. longum<\/jats:italic>\n                    420 with anti\u2010PD\u20101 and anti\u2010CTLA\u20104 antibodies resulted in stronger antitumor effects and improved survival compared with each monotherapy, without marked body weight loss. An empty\u2010vector control strain did not further enhance the efficacy of dual checkpoint blockade. Tumor analyses showed increased intratumoral CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell density and expansion of effector, central memory, and PD\u20101\n                    <jats:sup>+<\/jats:sup>\n                    Ki\u201067\n                    <jats:sup>+<\/jats:sup>\n                    proliferating CD8\n                    <jats:sup>+<\/jats:sup>\n                    subsets, together with treatment\u2010dependent differences in intratumoral CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell subset composition. These findings demonstrate that an oral WT1\u2010targeted Bifidobacterium vaccine can potentiate dual checkpoint blockade and promote a more immunologically active T cell landscape in PDAC. To our knowledge, this is the first demonstration of this combination strategy in a syngeneic pancreatic cancer model.\n                  <\/jats:p>","DOI":"10.1002\/advs.202524323","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:38:21Z","timestamp":1783420701000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["WT1\u2010Targeted Oral Bifidobacterium longum Vaccine Enhances Checkpoint Blockade Efficacy in Pancreatic Cancer"],"prefix":"10.1002","volume":"13","author":[{"given":"Taiki","family":"Yamazaki","sequence":"first","affiliation":[{"name":"Laboratory of Translational Research for Biologics, Department of Advanced Medical and Pharmaceutical Sciences Kobe University Graduate School of Science, Technology and Innovation Kobe 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