Strategies to develop therapeutic cancer vaccines for pancreatic cancer
Menée à partir d'une revue de 120 essais cliniques évaluant des vaccins thérapeutiques contre l'adénocarcinome canalaire du pancréas, cette synthèse qualitative examine la sécurité, la faisabilité et les limites du bénéfice clinique de différentes stratégies thérapeutiques (utilisation de microorganismes, de peptides, de protéines, d'acides nucléiques et de cellules) puis identifie les futurs axes de recherche
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 KRASmut, 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.
The Lancet Gastroenterology & Hepatology , résumé, 2026