Dual Adjuvant-Loaded Peptide Antigen Self-Assembly Potentiates Dendritic Cell-Mediated Tumor Immunotherapy

Clinical translation of current cancer vaccine research has been hampered by limited antitumor immune responses due to inefficient antigen delivery and presentation, suboptimal DC and T cell activation. Biomaterial-based nanovaccine offers targeted antigen delivery, protection from degradation in vi...

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Bibliographic Details
Published in:Advanced science 2024-09, Vol.11 (36), p.e2403663-n/a
Main Authors: Kim, Jaehyun, Kang, Seyoung, Kim, Jisu, Yong, Seok-Beom, Lahiji, Shayan Fakhraei, Kim, Yong-Hee
Format: Article
Language:English
Subjects:
Acids
Adjuvants
Antigen presentation
Apoptosis
Breast cancer
Cancer therapies
Cancer vaccines
Cytokines
Cytotoxicity
dendritic cell immunotherapy
Dendritic cells
Efficiency
immune checkpoint blockade
Immune system
Immunotherapy
Kinases
Lipids
Lymphatic system
Lymphocytes
Melanoma
Peptides
self‐assembly
therapeutic cancer vaccine
tumor‐associated antigen
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Summary:Clinical translation of current cancer vaccine research has been hampered by limited antitumor immune responses due to inefficient antigen delivery and presentation, suboptimal DC and T cell activation. Biomaterial-based nanovaccine offers targeted antigen delivery, protection from degradation in vivo, and prolonged tumor therapeutic efficacy. This study introduces a lipid-coated deoxycholic acid-survivin nanoassembly (DA-L-DSA). Survivin, overexpressed in several cancer cells and involved in cancer cell growth and immune evasion, is selected as a tumor-associated antigen. An major histocompatibility complex class I binding epitope of survivin is engineered into the nanoassembly. R848, TLR 7/8 agonist, and SD-208, TGF-beta receptor1 kinase inhibitor, are coencapsulated into the nanoassembly as potent adjuvants to boost DC maturation and enhance antigen presentation. The DA-L-DSA effectively stimulates the maturation of dendritic cells, migrates into lymph nodes, and enhances T-cell activation and Th1 response. A substantial influx of cytotoxic T lymphocytes into primary tumors is observed in a murine melanoma model and demonstrates anti-metastatic effects in a spontaneous breast cancer metastasis model. Furthermore, DA-L-DSA exhibits a remarkable synergistic effect in the combination therapy with immune checkpoint inhibitors alleviating immunosuppressive tumor microenvironment. Taken together, these findings suggest DA-L-DSA as a promising immuno-therapeutic platform that could be applicable to diverse intractable cancers.
ISSN:2198-3844
2198-3844
DOI:10.1002/advs.202403663