1. Controlling tumor progression and recurrence in mice through combined treatment with a PD-L1 inhibitor and a designer Salmonella strain that delivers GM-CSF
- Author
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Heung Jin Jeon, Daejin Lim, EunA So, Solbi Kim, Jae-Ho Jeong, Miryoung Song, and Hyo-Jin Lee
- Subjects
Checkpoint inhibitor ,Granulocyte macrophage colony stimulating factor ,Programmed death-ligand 1 ,Salmonella ,Therapeutics. Pharmacology ,RM1-950 - 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.
- Published
- 2024
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