Xiaodong Jiang, Viswanathan Muthusamy, Olga Fedorova, Yong Kong, Daniel J Kim, Marcus Bosenberg, Anna Marie Pyle, Akiko Iwasaki
{"title":"Intratumoral delivery of RIG-I agonist SLR14 induces robust antitumor responses.","authors":"Xiaodong Jiang, Viswanathan Muthusamy, Olga Fedorova, Yong Kong, Daniel J Kim, Marcus Bosenberg, Anna Marie Pyle, Akiko Iwasaki","doi":"10.1084/jem.20190801","DOIUrl":null,"url":null,"abstract":"<p><p>Cytosolic nucleic acid-sensing pathways can be triggered to enhance immune response to cancer. In this study, we tested the antitumor activity of a unique RIG-I agonist, stem loop RNA (SLR) 14. In the immunogenic tumor models, we observed significant tumor growth delay and an extended survival in SLR14-treated mice. SLR14 also greatly improved antitumor efficacy of anti-PD1 antibody over single-agent treatment. SLR14 was mainly taken up by CD11b<sup>+</sup> myeloid cells in the tumor microenvironment, and many genes associated with immune defense were significantly up-regulated after treatment, accompanied by increase in the number of CD8<sup>+</sup> T lymphocytes, NK cells, and CD11b<sup>+</sup> cells in SLR14-treated tumors. Strikingly, SLR14 dramatically inhibited nonimmunogenic B16 tumor growth, and the cured mice developed an immune memory. Furthermore, a systemic antitumor response was observed in both bilateral and tumor metastasis models. Collectively, our results demonstrate that SLR14 is a promising therapeutic RIG-I agonist for cancer treatment, either alone or in combination with existing immunotherapies.</p>","PeriodicalId":23015,"journal":{"name":"The Tokushima journal of experimental medicine","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2019-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1084/jem.20190801","citationCount":"43","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Tokushima journal of experimental medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1084/jem.20190801","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2019/10/10 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 43
Abstract
Cytosolic nucleic acid-sensing pathways can be triggered to enhance immune response to cancer. In this study, we tested the antitumor activity of a unique RIG-I agonist, stem loop RNA (SLR) 14. In the immunogenic tumor models, we observed significant tumor growth delay and an extended survival in SLR14-treated mice. SLR14 also greatly improved antitumor efficacy of anti-PD1 antibody over single-agent treatment. SLR14 was mainly taken up by CD11b+ myeloid cells in the tumor microenvironment, and many genes associated with immune defense were significantly up-regulated after treatment, accompanied by increase in the number of CD8+ T lymphocytes, NK cells, and CD11b+ cells in SLR14-treated tumors. Strikingly, SLR14 dramatically inhibited nonimmunogenic B16 tumor growth, and the cured mice developed an immune memory. Furthermore, a systemic antitumor response was observed in both bilateral and tumor metastasis models. Collectively, our results demonstrate that SLR14 is a promising therapeutic RIG-I agonist for cancer treatment, either alone or in combination with existing immunotherapies.