한빛사논문
- 조회377
Sang Nam Lee1, Sei Hyun Park1, Jin-Ho Choi1, Jang Hun Heo1, Min-Ho Lee2, Sang-Seok Oh2, Young-Woock Noh2, Yong Taik Lim1
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
2New Drug Development Center, Osong Medical Innovation Foundation, 123 Osongsaengmyeong-ro, Osong-eup. Heungdeok-gu, Cheongju, Chungbuk-do, 28160 Republic of Korea
Corresponding Author : Yong Taik Lim
Abstract
The heterologous immunity of live pathogens leads to the emergence of this approach as a pivotal component in cancer immunotherapy. However, virulence, inflammatory-related toxicity, and the induction of Treg cells after treatment hinder their clinical translation. Here, to exploit the heterologous immunity of live pathogens without risks, a virulence-free reconstituted synthetic nanopathogen (RSnP) is developed by the cell wall skeleton of disrupted Mycobacterium bovis and the incorporation of timely-activating Toll-like receptor 7/8 agonists of which multifaceted activities can be promoted by endolysosomal enzymes. Immunization with RSnP, even without tumor-specific antigens, exhibits potent antitumor efficacy against melanoma, breast cancer, and bladder cancer by promoting antitumor effector cells (CD8+ T cells, NK cells, M1 macrophages, and Th17 cells) and proinflammatory cytokines (IL-12p70, TNF-α, and IL-6) while simultaneously mitigating immunosuppressive myeloid cells (MDSCs and M2 macrophages) in the tumor microenvironment, surpassing the therapeutic efficacies of approved live-BCG drug and mRNA vaccine. The increase in CCR8+Foxp3+ Treg cells induced to counteract RSnP treatment can be attenuated by anti-CCR8 antibody, a depletion antibody for tumor-specific Treg cells, to synergize therapeutic efficacy with relieved autoimmunity. RSnP can be a therapeutic nanomedicine platform across heterologous cancers and emerging infectious virus variants with minimized toxicity.
논문정보
- Research article
- 2024년 11월 (BRIC 등록일 2024-11-07)
- 국내 연구진
- 의약학 > 면역의학
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