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Adv. Sci., Jul 29 2024, | https://doi.org/10.1002/advs.202403663
Dual Adjuvant-Loaded Peptide Antigen Self-Assembly Potentiates Dendritic Cell-Mediated Tumor Immunotherapy
Jaehyun Kim 1, Seyoung Kang 1, Jisu Kim 1, Seok-Beom Yong 2, Shayan Fakhraei Lahiji 1,3, Yong-Hee Kim 1,3,4
1Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea.
2Nucleic Acid Therapeutics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungcheongbuk-do, 28116, Republic of Korea.
3Cursus Bio Inc. Icure Tower, Seoul, 06170, Republic of Korea.
4Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University, Seoul, 04763, Republic of Korea.
Corresponding Author : Yong-Hee Kim
Abstract
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.
논문정보
- Research article
- 2024년 07월 (BRIC 등록일 2024-08-01)
- 국내 연구진
- 생명과학 > 생물공학
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