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Self‐Assembling Peptide‐Adjuvant Conjugate (SaPAC) Platform for Precision Cancer Immunotherapy
Open accessAbstract
Peptide cancer vaccines often suffer from poor lymphatic drainage, limited antigen‐presenting cell uptake, and weak innate immune activation. To overcome these barriers, we engineered the Self‐Assembling Peptide‐Adjuvant Conjugate (SaPAC) platform, which covalently links neoantigen epitopes to the TLR7 agonist 1V209 through site‐selective lysine conjugation. Synthesized by Fmoc solid‐phase peptide synthesis, SaPAC conjugates self‐assemble into cationic nanoparticles with hydrodynamic diameters of approximately 100–200 nm. Compared with unconjugated self‐assembling peptide nanoparticles mixed with soluble adjuvant, SaPAC nanoparticles enhanced lymphatic drainage and antigen persistence in draining lymph nodes. Mechanistically, SaPAC activated the TLR7‐MyD88 axis, promoted plasmacytoid dendritic cell and macrophage recruitment, drove APC maturation (CD80 + CD86 + ), and enhanced MHC‐I cross‐presentation to amplify antigen‐specific CD8+ T‐cell priming. Therapeutically, SaPAC monotherapy suppressed tumor growth in B16‐OVA melanoma and MB49 bladder carcinoma models by increasing intratumoral infiltration of activated CD8+ T cells and NK cells. In an orthotopic 4T1 triple‐negative breast cancer model, multivalent SaPAC vaccination synergized with anti‐PD‐1 blockade and achieved durable tumor suppression comparable to the Poly(I:C)‐adjuvanted benchmark without detectable systemic toxicity. Collectively, SaPAC represents a chemically defined platform that bridges innate and adaptive anti‐tumor immunity.
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From Sewer to Saviour—Targeting the Lymphatic System to Promote Drug Exposure and Activity
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Metadata
- Authors
- Wu, Y., Hu, J., Hu, Y., Li, W., Rong, L., Li, R., Yao, Y., Hu, L., Wang, X., Zhang, B., Lu, Y., Chow, S., Su, C., Yau, T., Chung, C. Y., & Huang, J.
- Affiliations
- University of Hong Kong (HK)
- School of Biomedical Sciences and School of Biomedical Engineering Li Ka Shing Faculty of Medicine The University of Hong Kong Pokfulam Hong Kong SAR People's Republic of China
- Hong Kong Science and Technology Parks Corporation (HK)
- Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences Shenzhen People's Republic of China
- Chinese Academy of Sciences (CN)
- Corresponding author
- Hu, Ye‐Fan
- Yau, Thomas
- Chung, Clive Yik‐Sham
- Huang, Jian‐Dong
- ORCID
- Venue
- Advanced Science
- Publisher
- Wiley
- Published
- 2026-10-02
- Pages
- e77632-e77632
- ISSN
- 2198-3844 (ISSN-L)
- PMC
- PMC13633104
- OpenAlex
- W7216274759
- Cited by
- 0
- References
- 2
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Advanced Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Key Research and Development Program of China (2021YFA0910700)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Keywords
- TLR7 agonist, cancer vaccine adjuvant, lymphatic drainage, antigen-presenting cell maturation, plasmacytoid dendritic cells, macrophage recruitment, CD8+ T cell priming, NK cell infiltration, anti-PD-1 combination therapy, melanoma, bladder cancer, triple-negative breast cancer
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