고원건 (연세대학교)

한빛사논문

조회216

연세대학교

CV File 52 kb

J. Control. Release, Jul 04 2024, S0168-3659(24)00435-8 | https://doi.org/10.1016/j.jconrel.2024.07.004 Tumor phagocytosis-driven STING activation invigorates antitumor immunity and reprograms the tumor micro-environment

Susam Lee^a,1, Kyeong Hee Hong ^b,c,1, Heewon Park ^a, JongHoon Ha ^a, Seung Eon Lee ^b, Dong Jin Park ^b,c, Seong Dong Jeong ^a, Seohyeon Kim^a, Dahae Kim ^b,c, JiWon Ahn ^b,c, Han-Woong Lee ^b,e, Won-Gun Koh ^d, Sang-Jun Ha^b,c, Yeu-Chun Kim ^a

^aDepartment of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea

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

^cBrain Korea 21 (BK21) FOUR Program, Yonsei Education & Research Center for Biosystems, Yonsei University, Seoul 03722, Republic of Korea

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

^eGEMCRO, Inc., Seoul 03722, Republic of Korea

¹These authors contributed equally.

Corresponding authors : Won-Gun Koh, Sang-Jun Ha, Yeu-Chun Kim

Abstract

Immunogenic cell death (ICD) holds the potential for in situ tumor vaccination while concurrently eradicating tumors and stimulating adaptive immunity. Most ICD inducers, however, elicit insufficient immune responses due to negative feedback against ICD biomarkers, limited infiltration of antitumoral immune cells, and the immunosuppressive tumor microenvironment (TME). Recent findings highlight the pivotal roles of stimulators of interferon gene (STING) activation, particularly in stimulating antigen-presenting cells (APCs) and TME reprogramming, addressing ICD limitations. Herein, we introduced 'tumor phagocytosis-driven STING activation', which involves the activation of STING in APCs during the recognition of ICD-induced cancer cells. We developed a polypeptide-based nanocarrier encapsulating both doxorubicin (DOX) and diABZI STING agonist 3 (dSA3) to facilitate this hypothesis in vitro and in vivo. After systemic administration, nanoparticles predominantly accumulated in tumor tissue and significantly enhanced anticancer efficacy by activating tumor phagocytosis-driven STING activation in MC38 and TC1 tumor models. Immunological activation of APCs occurred within 12 h, subsequently leading to the activation of T cells within 7 days, observed in both the TME and spleen. Furthermore, surface modification of nanoparticles with cyclic RGD (cRGD) moieties, which actively target integrin α _vβ ₃, enhances tumor accumulation and eradication, thereby verifying the establishment of systemic immune memory. Collectively, this study proposes the concept of tumor phagocytosis-driven STING activation and its effectiveness in generating short-term and long-term immune responses.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-16)
연구진국내 연구진
분야 생명과학 > 면역학

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