Strategies to develop therapeutic cancer vaccines for pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies. Conventional immunotherapies have shown little clinical benefit, largely due to the low neoantigenicity and profoundly immunosuppressive microenvironment of this cancer. Therapeutic cancer vaccines have emerged as a rational strategy to prime or amplify antitumour immunity, supported by advances in antigen discovery, genomic profiling, and vaccine engineering. Here, we report a review of clinical trials evaluating therapeutic cancer vaccines in PDAC. Eligible studies were identified through searches of ClinicalTrials.gov from database inception to Aug 31, 2025, with manual screening of trial-linked publications up to Jan 31, 2026. 135 records were identified, of which 120 met the eligibility criteria and were included in the qualitative synthesis. Across vaccine platforms-cell-based, nucleic acid-based, protein and peptide-based, microorganism-based, and multiplatform strategies-early-phase clinical studies consistently show feasibility, favourable safety profiles, and the induction of tumour-specific immune responses. However, immune activation has rarely translated into durable clinical benefit. To date, the most compelling biological signals derive from personalised neoantigen vaccines, particularly mRNA-based approaches, which can elicit high-magnitude CD8⁺ T-cell responses and long-lived clonal persistence in postoperative PDAC. Emerging evidence also supports the potential of shared neoantigens, such as KRAS^mut, as biologically relevant and scalable targets. Collectively, our findings highlight a shift towards rational vaccine combination strategies aimed at overcoming stromal and myeloid-mediated immunosuppression. Future progress will depend on integrating therapeutic vaccination into multimodal regimens and evaluating these approaches in adequately powered, biomarker-selected clinical trials.