Advances in vaccine-based therapies for pancreatic cancer Review
| Authors: | McMillan, M. T.; Soares, K. C. |
| Review Title: | Advances in vaccine-based therapies for pancreatic cancer |
| Abstract: | Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, with a 5-year survival rate that has improved only marginally over the past 30 years, despite numerous clinical trials. PDAC poses several unique challenges, including early metastatic spread and a predilection for liver metastasis. It is also highly resistant to anti-tumor immunity and immunotherapy due to its dense and immunosuppressive tumor microenvironment, low immunogenicity, and systemic immune suppression. PDAC has a low mutational burden, defective antigen presentation, and immune checkpoint molecule upregulation, which reduce immune recognition. Together, these factors leave PDAC as an “immune cold” tumor with minimal cytotoxic T-cell activity. Novel therapeutic approaches are urgently needed to reinvigorate anti-tumor immunity. Recent advances, such as adjuvant personalized mRNA neoantigen vaccines and mutant-KRAS targeted vaccines, have demonstrated sustained vaccine-induced T cell responses that are associated with improved recurrence-free survival in surgically resected PDAC. Combining different vaccine approaches with optimal sequencing of chemotherapy, surgery, radiotherapy, and other immunotherapies may further enhance outcomes. PDAC vaccines represent a promising strategy for overcoming PDAC’s resistance to conventional therapies, with ongoing trials exploring their potential to improve long-term survival. © The Author(s) 2025. |
| Keywords: | review; pancreas cancer; t lymphocyte; metastasis; antineoplastic activity; cancer inhibition; liver metastasis; antigen presentation; messenger rna; immunogenicity; antigen recognition; cytotoxic t lymphocyte; surgery; tumor immunity; upregulation; pancreatic cancer; immune deficiency; drug therapy; immunosuppressive treatment; therapy; vaccine; recurrence free survival; tumor microenvironment; pancreatic ductal adenocarcinoma; pancreatic ductal carcinoma; long term survival; rna vaccine; human; female; pdac; mrna vaccination; vaccine-based therapies |
| Journal Title: | Journal of Gastrointestinal Cancer |
| Volume: | 56 |
| ISSN: | 1941-6628 |
| Publisher: | Springer |
| Date Published: | 2025-02-12 |
| Start Page: | 62 |
| Language: | English |
| DOI: | 10.1007/s12029-025-01165-4 |
| PROVIDER: | scopus |
| PMCID: | PMC11821674 |
| PUBMED: | 39939414 |
| DOI/URL: | |
| Notes: | Review -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Kevin Soares -- Source: Scopus |
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