한빛사논문
- 조회57
Dinh-Huy Nguyen 1,2,3, Sung-Hwan You 4, Hien Thi-Thu Ngo 1,3,5, Khuynh Van Nguyen 1,3, Khang Vuong Tran 1,3, Tan-Huy Chu 6, So-young Kim 1,4, Sang-Jun Ha 7,*, Yeongjin Hong 1,3,4,8,* & Jung-Joon Min 1,2,3,4,*
1Institute for Molecular Imaging and Theranostics, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
2Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun 58128, Republic of Korea.
3Department of Biomedical Science (BrainKorea21 Plus) Chonnam National University Graduate School, Gwangju 61469, Republic of Korea.
4CNCure Co. Ltd, Hwasun 58128, Republic of Korea.
5Department of Biochemistry, Hanoi Medical University, Dong Da, No 1, Ton That Tung St., Hanoi 100000, Vietnam.
6Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
7Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
8Department of Microbiology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
*Corresponding authors: correspondence to Sang-Jun Ha, Yeongjin Hong or Jung-Joon Min
Abstract
Synergistic combinations of immunotherapeutic agents can improve the performance of anti-cancer therapies but may lead to immune-mediated adverse effects. These side-effects can be overcome by using a tumor-specific delivery system. Here, we report a method of targeted immunotherapy using an attenuated Salmonella typhimurium (SAM-FC) engineered to release dual payloads: cytolysin A (ClyA), a cytolytic anti-cancer agent, and Vibrio vulnificus flagellin B (FlaB), a potent inducer of anti-tumor innate immunity. Localized secretion of ClyA from SAM-FC induces immunogenic cancer cell death and promotes release of tumor-specific antigens and damage-associated molecular patterns, which establish long-term antitumor memory. Localized secretion of FlaB promotes phenotypic and functional remodeling of intratumoral macrophages that markedly inhibits tumor metastasis in mice bearing tumors of mouse and human origin. Both primary and metastatic tumors from bacteria-treated female mice are characterized by massive infiltration of anti-tumorigenic innate immune cells and activated tumor-specific effector/memory T cells; however, the percentage of immunosuppressive cells is low. Here, we show that SAM-FC induces functional reprogramming of the tumor immune microenvironment by activating both the innate and adaptive arms of the immune system and can be used for targeted delivery of multiple immunotherapeutic payloads for the establishment of potent and long-lasting antitumor immunity.
논문정보
- Research article
- 2024년 08월 (BRIC 등록일 2024-08-08)
- 국내(교신)+국외 연구진
- 의약학 > 종양의학
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