Designing a tumor landscape-modifying vaccine with a unique TLR2/6 agonist for refractory pancreatic cancer
Abstract Failure of cancer vaccines in clinical trials has been linked to poor preclinical translatability, immunosuppressive tumor microenvironments (TMEs), suboptimal antigen delivery to antigen-presenting cells, limited human MHC antigenicity, and insufficiently safe immune adjuvants. Therefore, this study aimed to design an integrated cancer vaccine and evaluate its efficacy in a KPC orthotopic pancreatic cancer model containing the G12D mutation. A novel immune adjuvant, C-VAX, was developed from the natural Toll-like receptor 2/6 agonist UNE-C1 and covalently linked to a KRAS G12D neoantigen and WNT5a, a tumor-associated antigen upregulated in resistant tumors. This integrated vaccine enhanced CD8⁺ T-cell infiltration and reduced α-SMA expression in the TME. The therapeutic effects were further enhanced following anti–PD-1 checkpoint blockade. These findings suggest that vaccines targeting tumor antigens and resistance-associated TME components may promote an immune-responsive TME in refractory cancers.
Authors
- S. Kim
- Uijoo Kim (ORCID: https://orcid.org/0009-0008-0916-6281)
- Hyeong Yun Kim (ORCID: https://orcid.org/0009-0006-8085-1383)
- Ji Hun Suh
- Do Sik Min (ORCID: https://orcid.org/0000-0002-8570-5098)
- Ee Chan Song (ORCID: https://orcid.org/0009-0008-7962-4188)
- Ina Yoon (ORCID: https://orcid.org/0000-0001-5307-3754)
- Yoonju Do
- Jiwon Kong (ORCID: https://orcid.org/0000-0003-3990-5619)
- Sung‐Hoon Kim (ORCID: https://orcid.org/0000-0002-1570-3230)
- Seongmin Cho (ORCID: https://orcid.org/0000-0003-1834-8972)
- Sunkyo Hwang
- Jeongwon Mun
- Hamin Ban
- Minju Kang (ORCID: https://orcid.org/0009-0006-9639-130X)
- JooHee Park
- Nayoung Kim
- Sang Bum Kim
- Hyun Seo Lee
- Hyo Eun Kim
- Eunhye Kwon
Institutions
- Yonsei University (KR)
- Sahmyook University (KR)
- Gangnam Severance Hospital (KR)
Publication Details
- Journal
- Cellular and Molecular Immunology
- Published
- 2026-10-27
- DOI
- https://doi.org/10.1038/s41423-026-01480-1
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministry of Trade, Industry and Energy
- Korea Institute for Advancement of Technology
- Korea Basic Science Institute
- National Research Foundation of Korea
- Ministry of SMEs and Startups
- Ministry of Science and ICT, South Korea