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Its clinical activity has also been documented in early phase clinical trials. The 5,6-dimethylxanthenone-4-acetic acid (DMXAA) stimulator of interferon genes (STING) agonist shows a comparable pattern of efficacy when used via intratumoral injections.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Mice subcutaneously engrafted with bilateral MC38 and B16.OVA-derived tumors were treated with proinflammatory immunotherapy agents known to be active when intratumorally delivered. The combination of BO-112 and DMXAA was chosen given its excellent efficacy and the requirements for antitumor effects were studied on selective depletion of immune cell types and in gene-modified mouse strains lacking basic leucine zipper ATF-like transcription factor 3 (BATF3), interferon-\u03b1\/\u03b2 receptor (IFNAR) or STING. Spatial requirements for the injections were studied in mice bearing three tumor lesions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>BO-112 and DMXAA when co-injected in one of the lesions of mice bearing concomitant bilateral tumors frequently achieved complete local and distant antitumor efficacy. Synergistic effects were contingent on CD8 T cell lymphocytes and dependent on conventional type 1 dendritic cells, responsiveness to type I interferon (IFN) and STING function in the tumor-bearing host. Efficacy was preserved even if BO-112 and DMXAA were injected in separate lesions in a manner able to control another untreated third-party tumor. Efficacy could be further enhanced on concurrent PD-1 blockade.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Clinically feasible co-injections of BO-112 and a STING agonist attain synergistic efficacy able to eradicate distant untreated tumor lesions.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2021-002953","type":"journal-article","created":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T11:30:56Z","timestamp":1637839856000},"page":"e002953","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":38,"title":["Intratumoral co-injection of the poly I:C-derivative BO-112 and a STING agonist synergize to achieve local and distant anti-tumor efficacy"],"prefix":"10.1136","volume":"9","clinical-trial-number":[{"clinical-trial-number":"nct04525859","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04420975","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04508140","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5969-9181","authenticated-orcid":false,"given":"Maite","family":"Alvarez","sequence":"first","affiliation":[{"name":"Immunology and Immunotherapy, Center for Applied Medical Research (CIMA). 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