이효진 (충남대학교 의과대학, 충남대학교병원)

한빛사논문

조회270

충남대학교 의과대학, 충남대학교병원

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Acta Pharm. Sin. B, Available online 10 July 2024 | https://doi.org/10.1016/j.apsb.2024.07.011 Controlling tumor progression and recurrence in mice through combined treatment with a PD-L1 inhibitor and a designer Salmonella strain that delivers GM-CSF

Heung Jin Jeon ^a†, Daejin Lim ^b†, EunA So ^c, Solbi Kim ^d, Jae-Ho Jeong^c, Miryoung Song ^e, Hyo-Jin Lee^a,d,f

^aInfection Control Convergence Research Center, Chungnam National University College of Medicine, Daejeon, Republic of Korea

^bDivision of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea

^cDepartment of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea

^dDepartment of Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea

^eDepartment of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yongin, Republic of Korea

^fDepartment of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea

^†These authors made equal contributions to this journal.

Corresponding authors : Jae-Ho Jeong, Miryoung Song, Hyo-Jin Lee

Abstract

Combination therapy with checkpoint inhibitors blocks inhibitory immune cell signaling and improves clinical responses to anticancer treatments. However, continued development of innovative and controllable delivery systems for immune-stimulating agents is necessary to optimize clinical responses. Herein, we engineered Salmonella to deliver recombinant granulocyte macrophage colony stimulating factor (GM-CSF) in a controllable manner for combination treatment with a programmed death-ligand 1 (PD-L1) inhibitor. The engineered Salmonella enabled delivery of recombinant GM-CSF into mouse tumors, activating recruitment of immune cells, such as M1-polarized macrophages, dendritic cells, and CD8+ T cells. Combination treatment with the PD-L1 inhibitor and engineered Salmonella increased the survival rate of tumor-bearing mice by 25%. New tumor growth was strongly suppressed, and visible tumors disappeared at 120 days post-infection (dpi) in mice rechallenged with additional tumor implantation at 100 dpi. The number of memory T cells increased >2-fold in tumor-rechallenged mice. Our findings demonstrate superiority of the engineered Salmonella as a cancer therapeutic agent with precise targeting ability, immune-boosting activity, and ease of combination with other therapeutics.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-19)
연구진국내 연구진
분야 의약학 > 종양의학

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