한빛사논문
- 조회431
Hong Sik Shin 1, Sohyun Kim 1, Seung Mo Jin 1, Yeon Jeong Yoo 1, Jang Hun Heo 1, Yong Taik Lim 1
1SKKU Advanced Institute of Nanotechnology (SAINT), Department of Nano Science and Technology, Department of Nano Engineering, School of Chemical Engineering, Sungkyunkwan University (SKKU), 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do, 16419, Republic of Korea.
H. S. Shin and S. H. Kim contributed equally to this study.
CORRESPONDING AUTHOR : Yong Taik Lim
Abstract
Activation of the innate immune system counteracts tumor-induced immunosuppression. Hence, small molecule-based Toll-like receptor 7/8 agonists (TLR7/8a), which can modulate immunosuppression in the tumor microenvironment along with the activation of innate immunity, are emerging as essential components of cancer immunotherapy. However, the clinical application of synthetic TLR7/8a therapies has been limited by systemic immune-associated toxicity and immune tolerance induced by uncontrolled stimulatory activities and repeated treatments. To address these limitations, a dynamic immunomodulation strategy incorporating masking and temporal recovery of the activity of TLR7/8a through prodrug-like TLR7/8a (pro-TLR7/8a) at the molecular level and a sustained and controlled release of active TLR7/8a from nanoliposome (pro-TLR7/8a) (NL(pro-TLR7/8)) in a macroscale depot were designed. Immunization with cationic NL(pro-TLR7/8) and anionic antigens triggered robust activation of innate immune cells as well as antigen-specific T cell responses, eliciting reprogramming of immunosuppressive cells (M2 macrophages and MDSCs) into tumor-suppressive cells (M1 macrophages), with decreased systemic adverse effects and immune tolerance. Combination treatment with NL(pro-TLR7/8a) and immune checkpoint inhibitors (anti-CTLA-4 plus anti-PD-L1) or nanoliposomes (Dox) had synergistic effects on antitumor immunity in various tumor models. The concept of pro-TLR7/8a suggested herein may facilitate the advancement of small-molecule-based immunomodulators for clinical translation and safe and effective cancer immunotherapy.
논문정보
- Research article
- 2023년 10월 (BRIC 등록일 2023-11-02)
- 국내 연구진
- 바이오·의료융합 > 바이오소재
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