ExoSTING, an extracellular vesicle loaded with STING agonists, promotes tumor immune surveillance
Cyclic dinucleotide (CDN) agonists of the STimulator of InterferoN Genes (STING) pathway have shown immune activation and tumor clearance in pre-clinical models. However, CDNs administered intratumorally also promote STING activation leading to direct cytotoxicity of many cell types in the tumor mic...
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| Veröffentlicht in: | Communications biology 2021-04, Vol.4 (1), p.497-497, Article 497 |
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| creator | Jang, Su Chul Economides, Kyriakos D. Moniz, Raymond J. Sia, Chang Ling Lewis, Nuruddeen McCoy, Christine Zi, Tong Zhang, Kelvin Harrison, Rane A. Lim, Joanne Dey, Joyoti Grenley, Marc Kirwin, Katherine Ross, Nikki L. Bourdeau, Raymond Villiger-Oberbek, Agata Estes, Scott Xu, Ke Sanchez-Salazar, Jorge Dooley, Kevin Dahlberg, William K. Williams, Douglas E. Sathyanarayanan, Sriram |
| description | Cyclic dinucleotide (CDN) agonists of the STimulator of InterferoN Genes (STING) pathway have shown immune activation and tumor clearance in pre-clinical models. However, CDNs administered intratumorally also promote STING activation leading to direct cytotoxicity of many cell types in the tumor microenvironment (TME), systemic inflammation due to rapid tumor extravasation of the CDN, and immune ablation in the TME. These result in a failure to establish immunological memory. ExoSTING, an engineered extracellular vesicle (EV) exogenously loaded with CDN, enhances the potency of CDN and preferentially activates antigen presenting cells in the TME. Following intratumoral injection, exoSTING was retained within the tumor, enhanced local Th1 responses and recruitment of CD8
+
T cells, and generated systemic anti-tumor immunity to the tumor. ExoSTING at therapeutically active doses did not induce systemic inflammatory cytokines, resulting in an enhanced therapeutic window. ExoSTING is a novel, differentiated therapeutic candidate that leverages the natural biology of EVs to enhance the activity of CDNs.
Su Chul Jang et al. develop exoSTING, consisting of an engineered extracellular vesicle loaded with a potent cyclic dinucleotide (CDN) agonist of the STING pathway. They find that exoSTING shows more than 100-fold increased potency in in vivo tumor models and has increased tumor retention and lower levels of systemic inflammatory cytokine production as compared to free CDN. |
| doi_str_mv | 10.1038/s42003-021-02004-5 |
| format | Article |
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+
T cells, and generated systemic anti-tumor immunity to the tumor. ExoSTING at therapeutically active doses did not induce systemic inflammatory cytokines, resulting in an enhanced therapeutic window. ExoSTING is a novel, differentiated therapeutic candidate that leverages the natural biology of EVs to enhance the activity of CDNs.
Su Chul Jang et al. develop exoSTING, consisting of an engineered extracellular vesicle loaded with a potent cyclic dinucleotide (CDN) agonist of the STING pathway. They find that exoSTING shows more than 100-fold increased potency in in vivo tumor models and has increased tumor retention and lower levels of systemic inflammatory cytokine production as compared to free CDN.</description><identifier>ISSN: 2399-3642</identifier><identifier>EISSN: 2399-3642</identifier><identifier>DOI: 10.1038/s42003-021-02004-5</identifier><identifier>PMID: 33888863</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/106 ; 13/21 ; 13/31 ; 13/51 ; 14/28 ; 14/34 ; 38/32 ; 38/39 ; 38/77 ; 38/90 ; 38/91 ; 631/61/350/354 ; 631/67/1059/2325 ; 64/110 ; 64/60 ; 82/29 ; 82/80 ; 82/83 ; Ablation ; Agonists ; Antigen-presenting cells ; Antigens ; Biology ; Biomedical and Life Sciences ; Cancer ; CD8 antigen ; Cytokines ; Cytotoxicity ; Extravasation ; Immune clearance ; Immunological memory ; Immunosurveillance ; Immunotherapy ; Inflammation ; Interferon ; Life Sciences ; Life Sciences & Biomedicine ; Life Sciences & Biomedicine - Other Topics ; Lymphocytes ; Lymphocytes T ; Multidisciplinary Sciences ; Science & Technology ; Science & Technology - Other Topics ; Tumor microenvironment</subject><ispartof>Communications biology, 2021-04, Vol.4 (1), p.497-497, Article 497</ispartof><rights>The Author(s) 2021</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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However, CDNs administered intratumorally also promote STING activation leading to direct cytotoxicity of many cell types in the tumor microenvironment (TME), systemic inflammation due to rapid tumor extravasation of the CDN, and immune ablation in the TME. These result in a failure to establish immunological memory. ExoSTING, an engineered extracellular vesicle (EV) exogenously loaded with CDN, enhances the potency of CDN and preferentially activates antigen presenting cells in the TME. Following intratumoral injection, exoSTING was retained within the tumor, enhanced local Th1 responses and recruitment of CD8
+
T cells, and generated systemic anti-tumor immunity to the tumor. ExoSTING at therapeutically active doses did not induce systemic inflammatory cytokines, resulting in an enhanced therapeutic window. ExoSTING is a novel, differentiated therapeutic candidate that leverages the natural biology of EVs to enhance the activity of CDNs.
Su Chul Jang et al. develop exoSTING, consisting of an engineered extracellular vesicle loaded with a potent cyclic dinucleotide (CDN) agonist of the STING pathway. They find that exoSTING shows more than 100-fold increased potency in in vivo tumor models and has increased tumor retention and lower levels of systemic inflammatory cytokine production as compared to free CDN.</description><subject>13/1</subject><subject>13/106</subject><subject>13/21</subject><subject>13/31</subject><subject>13/51</subject><subject>14/28</subject><subject>14/34</subject><subject>38/32</subject><subject>38/39</subject><subject>38/77</subject><subject>38/90</subject><subject>38/91</subject><subject>631/61/350/354</subject><subject>631/67/1059/2325</subject><subject>64/110</subject><subject>64/60</subject><subject>82/29</subject><subject>82/80</subject><subject>82/83</subject><subject>Ablation</subject><subject>Agonists</subject><subject>Antigen-presenting cells</subject><subject>Antigens</subject><subject>Biology</subject><subject>Biomedical and Life Sciences</subject><subject>Cancer</subject><subject>CD8 antigen</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Extravasation</subject><subject>Immune clearance</subject><subject>Immunological memory</subject><subject>Immunosurveillance</subject><subject>Immunotherapy</subject><subject>Inflammation</subject><subject>Interferon</subject><subject>Life Sciences</subject><subject>Life Sciences & Biomedicine</subject><subject>Life Sciences & Biomedicine - Other Topics</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Multidisciplinary Sciences</subject><subject>Science & Technology</subject><subject>Science & Technology - Other Topics</subject><subject>Tumor 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activation and tumor clearance in pre-clinical models. However, CDNs administered intratumorally also promote STING activation leading to direct cytotoxicity of many cell types in the tumor microenvironment (TME), systemic inflammation due to rapid tumor extravasation of the CDN, and immune ablation in the TME. These result in a failure to establish immunological memory. ExoSTING, an engineered extracellular vesicle (EV) exogenously loaded with CDN, enhances the potency of CDN and preferentially activates antigen presenting cells in the TME. Following intratumoral injection, exoSTING was retained within the tumor, enhanced local Th1 responses and recruitment of CD8
+
T cells, and generated systemic anti-tumor immunity to the tumor. ExoSTING at therapeutically active doses did not induce systemic inflammatory cytokines, resulting in an enhanced therapeutic window. ExoSTING is a novel, differentiated therapeutic candidate that leverages the natural biology of EVs to enhance the activity of CDNs.
Su Chul Jang et al. develop exoSTING, consisting of an engineered extracellular vesicle loaded with a potent cyclic dinucleotide (CDN) agonist of the STING pathway. They find that exoSTING shows more than 100-fold increased potency in in vivo tumor models and has increased tumor retention and lower levels of systemic inflammatory cytokine production as compared to free CDN.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33888863</pmid><doi>10.1038/s42003-021-02004-5</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0003-2202-1980</orcidid><orcidid>https://orcid.org/0000-0001-8955-9684</orcidid><orcidid>https://orcid.org/0000-0003-3326-1007</orcidid><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_webofscience_primary_000644275500007 |
| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; Nature Free; Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; PubMed Central; Springer Nature OA/Free Journals |
| subjects | 13/1 13/106 13/21 13/31 13/51 14/28 14/34 38/32 38/39 38/77 38/90 38/91 631/61/350/354 631/67/1059/2325 64/110 64/60 82/29 82/80 82/83 Ablation Agonists Antigen-presenting cells Antigens Biology Biomedical and Life Sciences Cancer CD8 antigen Cytokines Cytotoxicity Extravasation Immune clearance Immunological memory Immunosurveillance Immunotherapy Inflammation Interferon Life Sciences Life Sciences & Biomedicine Life Sciences & Biomedicine - Other Topics Lymphocytes Lymphocytes T Multidisciplinary Sciences Science & Technology Science & Technology - Other Topics Tumor microenvironment |
| title | ExoSTING, an extracellular vesicle loaded with STING agonists, promotes tumor immune surveillance |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-11T13%3A59%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_webof&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=ExoSTING,%20an%20extracellular%20vesicle%20loaded%20with%20STING%20agonists,%20promotes%20tumor%20immune%20surveillance&rft.jtitle=Communications%20biology&rft.au=Jang,%20Su%20Chul&rft.date=2021-04-22&rft.volume=4&rft.issue=1&rft.spage=497&rft.epage=497&rft.pages=497-497&rft.artnum=497&rft.issn=2399-3642&rft.eissn=2399-3642&rft_id=info:doi/10.1038/s42003-021-02004-5&rft_dat=%3Cproquest_webof%3E2516596780%3C/proquest_webof%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2516596780&rft_id=info:pmid/33888863&rft_doaj_id=oai_doaj_org_article_d6164d29cedd4b8db922002838b3e600&rfr_iscdi=true |