The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers
Open accessAbstract
Tumor-associated macrophages (TAMs) usually express an M2 phenotype, which enables them to perform immunosuppressive and tumor-promoting functions. Reprogramming these TAMs toward an M1 phenotype could thwart their pro-cancer activities and unleash anti-tumor immunity, but efforts to accomplish this are nonspecific and elicit systemic inflammation. Here we describe a targeted nanocarrier that can deliver in vitro-transcribed mRNA encoding M1-polarizing transcription factors to reprogram TAMs without causing systemic toxicity. We demonstrate in models of ovarian cancer, melanoma, and glioblastoma that infusions of nanoparticles formulated with mRNAs encoding interferon regulatory factor 5 in combination with its activating kinase IKKβ reverse the immunosuppressive, tumor-supporting state of TAMs and reprogram them to a phenotype that induces anti-tumor immunity and promotes tumor regression. We further establish that these nanoreagents are safe for repeated dosing. Implemented in the clinic, this immunotherapy could enable physicians to obviate suppressive tumors while avoiding systemic treatments that disrupt immune homeostasis.
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Cites
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The clinical progress of mRNA vaccines and immunotherapies
Barbier, A. J., Jiang, A. Y., Zhang, P., Wooster, R., & Anderson, D. G. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01294-2 · Cited by 823
Macrophage-Based Approaches for Cancer Immunotherapy
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Immunomodulation‐Enhanced Nanozyme‐Based Tumor Catalytic Therapy
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Metadata
- Authors
- Zhang, F., Parayath, N. N., Ene, C. I., Stephan, S. B., Koehne, A. L., Coon, M. E., Holland, E. C., & Stephan, M. T.
- Venue
- Nature Communications
- Published
- 2019-09-03
- Volume
- 10
- Issue
- 1
- Pages
- 3974-3974
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2971468927
- Cited by
- 521
- References
- 71
- FWCI
- 18.27
- Type
- journal article
- Language
- en
- Open access
- gold
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- Zhang, F., Parayath, N. N., Ene, C. I., Stephan, S. B., Koehne, A. L., Coon, M. E., Holland, E. C., & Stephan, M. T. (2019). Genetic programming of macrophages to perform anti-tumor functions using targeted mRNA nanocarriers. Nature Communications. https://doi.org/10.1038/s41467-019-11911-5
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