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김태현Taihyun Kim

연세대학교

Nano Today, Available online 27 March 2024 | https://doi.org/10.1016/j.nantod.2024.102237 Immortalized nanodendritic cells decorated with immune-checkpoint inhibitors for personalized cancer immunotherapy

Daheui Choi ^a,1, Tae Gun Kang ^b,1, Taihyun Kim ^a,1, Chae-Won Moon ^b,1, Moonhyun Choi ^a, Da-Hae Kim ^b, Taeho Kim ^a, Yoogyeong Oh ^a, Sungwon Jung ^a, Yoojin Lee ^a, Sangmin Lee ^c, Jinkee Hong ^a, Sang-Jun Ha ^b

^aDepartment of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Republic of Korea

^bDepartment of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea

^cSchool of Mechanical Engineering, Chung-ang University, Seoul 06974, Republic of Korea

¹These authors contributed equally to this work as a first author.

Corresponding authors : Jinkee Hong, Sang-Jun Ha

Abstract

In our study, we have designated artificial nanoDCs (anDCs) by transferring the whole DC membrane onto the gold nanoparticles (Au NPs) to overcome the limitation of DC therapy. The anDCs were optimized by varying membrane-to-substrate ratio, exhibiting similar features with natural DC in having a T cell stimulation and tumor regression even after long-term stability of up to 30 days. This versatile anDCs platform allows engineering immune-boosting agents onto their surface on demand. We further functionalized one of the immune checkpoint inhibitors (ICI), αCTLA-4, on anDCs, leading to complete tumor clearance compared to DC membrane vesicles. Surprisingly, αCTLA-4 conjugated anDC (αCTLA-4-anDC) dramatically blocked the CTLA-4 pathway and resulted in increased frequency and effector cytokine functions in cytotoxic CD8+ T cells. Thus, our anDC system can effectively induce a tumor-specific T cell immune response by sustainable and potent T cell priming ability based on the high stability of anDCs, suggesting a great potential platform for next-generation personalized cancer immunotherapy.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-04-17)
연구진국내 연구진
분야 생명과학 > 면역학

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