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Nanoparticle-STING Agonist Enhances the Tumoricidal Effect of Bone Marrow-Derived Macrophage

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abstract
The stimulator of interferon genes (STING) pathway presents tremendous promise in the realm of cancer treatment because of its essential role in promoting antitumor immune responses. Our lab has recently developed an immunotherapeutic nanoparticle (NPcGAMP) that is capable of STING pathway activation. NP-cGAMP has an ability to deliver STING agonist (cGAMP) to bind to STING in cytosol and induce the production of type I interferons (IFNs) and other proinflammatory cytokines. This study investigated the immunological effects of NP-cGAMP on macrophages and tested if NP-cGAMP could boost macrophages’ tumor killing ability.The STING activation was evaluated and confirmed by measuring type I IFNs and proinflammatory cytokines through real-time qPCR and ELISA assays. Expression of CD86 and MHC II on macrophages, the maturation and activation markers, was determined by flow cytometry. NP-cGAMP enhanced antitumor effects of bone marrowderived macrophage (BMDM) against non-small cell lung cancer (NSCLC) Lewis lung cancer (LLC) and CMT-167 cells, and mesothelioma AB1 cells were examined using the CytoTox 96 Non-radioactive Cytotoxicity Assay. Overall, our study demonstrated that NP-cGAMP effectively activated the STING pathway and stimulated BMDM maturation. Additionally, the treatment with NP-cGAMP enhanced the tumor killing ability of macrophages against all three tumor cell lines.
subject
Exogenous STING agonist
Lung cancer
Macrophage activation
Proinflammatory cytokine production
STING pathway activation
Tumor-killing ability
contributor
Yuan, Xuanzhen (author)
Zhao, Dawen (committee chair)
Lu, Yong (committee member)
Lee, Yong Woo (committee member)
date
2021-09-01T08:35:44Z (accessioned)
2021-09-01T08:35:44Z (available)
2021 (issued)
degree
Biomedical Engineering (discipline)
identifier
http://hdl.handle.net/10339/99076 (uri)
language
en (iso)
publisher
Wake Forest University
title
Nanoparticle-STING Agonist Enhances the Tumoricidal Effect of Bone Marrow-Derived Macrophage
type
Thesis

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