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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Veröffentlicht in:Advanced science Jg. 11; H. 36; S. e2403663 - n/a
Hauptverfasser: Kim, Jaehyun, Kang, Seyoung, Kim, Jisu, Yong, Seok‐Beom, Lahiji, Shayan Fakhraei, Kim, Yong‐Hee
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Germany John Wiley & Sons, Inc 01.09.2024
John Wiley and Sons Inc
Wiley
Schlagworte:
Acids
Adjuvants
Adjuvants, Immunologic - administration & dosage
Adjuvants, Immunologic - pharmacology
Animals
Antigen presentation
Antigens, Neoplasm - immunology
Apoptosis
Breast cancer
Cancer therapies
Cancer vaccines
Cancer Vaccines - administration & dosage
Cancer Vaccines - immunology
Cytokines
Cytotoxicity
dendritic cell immunotherapy
Dendritic cells
Dendritic Cells - immunology
Disease Models, Animal
Efficiency
Female
Humans
immune checkpoint blockade
Immune system
Immunotherapy
Immunotherapy - methods
Kinases
Lipids
Lymphatic system
Lymphocytes
Melanoma
Mice
Mice, Inbred C57BL
Peptides
Peptides - chemistry
Peptides - immunology
self‐assembly
Survivin - immunology
therapeutic cancer vaccine
tumor‐associated antigen
tumor‐associated antigen
dendritic cell immunotherapy
immune checkpoint blockade
self‐assembly
therapeutic cancer vaccine
ISSN:2198-3844, 2198-3844
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Zusammenfassung: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. This study demonstrates the efficacy of dendritic cell‐mediated anticancer immunotherapy in allograft melanoma models and metastatic breast cancer models by producing major histocompatibility complex (MHC) I binding peptide epitopes of survivin proteins expressed in various cancers in the form of self‐assembled nanostructures with dual adjuvants.
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ISSN:2198-3844
2198-3844
DOI:10.1002/advs.202403663