The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Endosomolytic polymersomes increase the activity of cyclic dinucleotide STING agonists to enhance cancer immunotherapy
Open accessAbstract
Cyclic dinucleotide (CDN) agonists of stimulator of interferon genes (STING) are a promising class of immunotherapeutics that activate innate immunity to increase tumour immunogenicity. However, the efficacy of CDNs is limited by drug delivery barriers, including poor cellular targeting, rapid clearance and inefficient transport to the cytosol where STING is localized. Here, we describe STING-activating nanoparticles (STING-NPs)—rationally designed polymersomes for enhanced cytosolic delivery of the endogenous CDN ligand for STING, 2′3′ cyclic guanosine monophosphate–adenosine monophosphate (cGAMP). STING-NPs increase the biological potency of cGAMP, enhance STING signalling in the tumour microenvironment and sentinel lymph node, and convert immunosuppressive tumours to immunogenic, tumoricidal microenvironments. This leads to enhanced therapeutic efficacy of cGAMP, inhibition of tumour growth, increased rates of long-term survival, improved response to immune checkpoint blockade and induction of immunological memory that protects against tumour rechallenge. We validate STING-NPs in freshly isolated human melanoma tissue, highlighting their potential to improve clinical outcomes of immunotherapy.Rationally designed polymer vesicles increase cytosolic delivery of cGAMP, activating the STING pathway and increasing the immunogenicity of the tumour microenvironment in in vivo murine models of melanoma and in human metastatic melanoma tissues.
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cGAS-STING, an important pathway in cancer immunotherapy
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Activating cGAS-STING pathway for the optimal effect of cancer immunotherapy
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Metadata
- Authors
- Shae, D., Becker, K. W., Christov, P., Yun, D. S., Lytton-Jean, A. K. R., Sevimli, S., Ascano, M., Kelley, M., Johnson, D. B., Balko, J. M., & Wilson, J. T.
- Venue
- Nature Nanotechnology
- Published
- 2019-01-21
- Volume
- 14
- Issue
- 3
- Pages
- 269-278
- ISSN
- 1748-3387 (ISSN-L)
- 1748-3395
- OpenAlex
- W2909554490
- Cited by
- 668
- References
- 57
- FWCI
- 22.27
- Type
- journal article
- Language
- en
- Open access
- green
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- Shae, D., Becker, K. W., Christov, P., Yun, D. S., Lytton-Jean, A. K. R., Sevimli, S., Ascano, M., Kelley, M., Johnson, D. B., Balko, J. M., & Wilson, J. T. (2019). Endosomolytic polymersomes increase the activity of cyclic dinucleotide STING agonists to enhance cancer immunotherapy. Nature Nanotechnology. https://doi.org/10.1038/s41565-018-0342-5
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