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|a 10.1002/adma.202406140
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|a eng
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|a Wu, Leyang
|e verfasserin
|4 aut
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| 245 |
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|a Dual-Engineered Macrophage-Microbe Encapsulation for Metastasis Immunotherapy
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|c 2024
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|a Text
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|a ƒaComputermedien
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|a Date Completed 18.09.2024
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|a Date Revised 18.09.2024
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a © 2024 Wiley‐VCH GmbH.
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|a Lung metastases are the leading cause of death among cancer patients. The challenges of inefficient drug delivery, compounded by a robust immunosuppressive microenvironment, make effective treatment difficult. Here, an innovative dual-engineered macrophage-microbe encapsulation (Du-EMME) therapy is developed that integrates modified macrophages and engineered antitumor bacteria. These engineered macrophages, termed R-GEM cells, are designed to express RGD peptides on extracellular membranes, enhancing their tumor cell binding and intratumor enrichment. R-GEM cells are cocultured with attenuated Salmonella typhimurium VNP20009, producing macrophage-microbe encapsulation (R-GEM/VNP cells). The intracellular bacteria maintain bioactivity for more than 24 h, and the bacteria released from R-GEM/VNP cells within the tumor continue to exert bacteria-mediated antitumor effects. This is further supported by macrophage-based chemotaxis and camouflage, which enhance the intratumoral enrichment and biocompatibility of the bacteria. Additionally, R-GEM cells loaded with IFNγ-secreting strains (VNP-IFNγ) form R-GEM/VNP-IFNγ cells. Treatment with these cells effectively halts lung metastatic tumor progression in three mouse models (breast cancer, melanoma, and colorectal cancer). R-GEM/VNP-IFNγ cells vigorously activate the tumor microenvironment, suppressing tumor-promoting M2-type macrophages, MDSCs, and Tregs, and enhancing tumor-antagonizing M1-type macrophages, mature DCs, and Teffs. Du-EMME therapy offers a promising strategy for targeted and enhanced antitumor immunity in treating cancer metastases
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|a Journal Article
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|a engineered macrophages
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|a immune activation
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|a microbial therapeutics
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|a salmonella typhimurium VNP20009
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|a tumor‐targeted delivery
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| 700 |
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|a Qiao, Liyuan
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| 700 |
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|a Zhang, Shuhui
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|4 aut
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| 700 |
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|a Qiu, Jiahui
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|a Du, Zengzheng
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|a Sun, Ying
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| 700 |
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|a Chang, Xiaoyao
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|a Li, Lin
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| 700 |
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|a Li, Chenyang
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| 700 |
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|a Qiao, Xinyue
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| 700 |
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|a Yin, Xingpeng
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| 700 |
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|a Hua, Zichun
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| 773 |
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|i Enthalten in
|t Advanced materials (Deerfield Beach, Fla.)
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|g 36(2024), 36 vom: 01. Sept., Seite e2406140
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|u http://dx.doi.org/10.1002/adma.202406140
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