{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:05:41Z","timestamp":1782281141943,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100022752","name":"MSD Sharp and Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100022752","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP2008287"],"award-info":[{"award-number":["APP2008287"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020542","name":"Arthritis Queensland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Cancer vaccines combine tumor antigen and adjuvant to drive an anti\u2010tumor immune response. Clec9A\u2010targeted nanoparticles directing CD4 and CD8 neo\u2010epitopes to cross\u2010presenting dendritic cells (DCs) stimulate adjuvant\u2010free therapeutically effective tumor\u2010specific immunity. However, personalised neo\u2010epitopes limit the scalability of Clec9A nanoparticles for clinical translation. Since Clec9A\n                      <jats:sup>+<\/jats:sup>\n                      DCs constitutively present relevant neoepitopes in tumors but are suppressed in tumor microenvironments, we developed Clec9A\u2010targeted STING or RIG\u2010I liposomes to enhance endogenous tumor immunity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Liposomes encapsulating RIG\u2010I or the STING agonist MSA\u20101 and functionalised with Clec9A binding peptide WH were optimised for uptake by Clec9A\n                      <jats:sup>+<\/jats:sup>\n                      conventional and plasmacytoid DCs\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Biodistribution after i.v. administration was determined with\n                      <jats:italic>in vivo<\/jats:italic>\n                      imaging and cellular uptake and activation with flow cytometry. Plasma was analysed for type 1 interferon (IFN) by ELISA and liver, spleen, tumor, blood, kidney, heart and tumor draining lymph node transcriptomes were analysed with Nanostring. Effects on tumor growth and survival, and tumor\u2010specific T\u00a0cells were evaluated using the B16 melanoma model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Clec9A\u2010targeting liposomes administered i.v. were distributed to spleen, liver and tumor and were taken up by cross\u2010presenting and plasmacytoid DCs. Type 1 IFN production and DC, B\u2010 and T\u2010cell activation were more effective with i.v. Clec9A\u2010STING than Clec9A\u2010RIG\u2010I liposomes. Intravenous Clec9A\u2010STING liposomes stimulated IFN\u2010dependent transcription in blood, lung, tumor, and draining lymph nodes. Intravenous Clec9A\u2010STING liposomes, or intra\u2010tumoral Clec9A\u2010RIG\u2010I liposomes significantly suppressed B16\u2010F10 melanoma growth and induced neo\u2010epitope and survivin\u2010specific CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Clec9A\u2010STING liposomes are a scalable, translatable tumor\u2010targeted immunotherapy platform.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cti2.70110","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:32:36Z","timestamp":1780381956000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Control of poorly immunogenic tumors with systemic\n                    <scp>STING<\/scp>\n                    agonist\u2010loaded liposomes targeting cross\u2010presenting dendritic cells"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6199-0584","authenticated-orcid":false,"given":"Bijun","family":"Zeng","sequence":"first","affiliation":[{"name":"Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6450-9055","authenticated-orcid":false,"given":"Meghna","family":"Talekar","sequence":"additional","affiliation":[{"name":"Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8030-9053","authenticated-orcid":false,"given":"Thais","family":"Aragao\u2010Horoiwa","sequence":"additional","affiliation":[{"name":"Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7648-1803","authenticated-orcid":false,"given":"Amy","family":"Cameron","sequence":"additional","affiliation":[{"name":"Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0541-3125","authenticated-orcid":false,"given":"Guangzu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Zybina","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Blumenschein","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karyn","family":"van de Mark","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8423-1014","authenticated-orcid":false,"given":"Wittaya","family":"Suwakulsiri","sequence":"additional","affiliation":[{"name":"Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gretchen A","family":"Baltus","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  Rahway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1625-9853","authenticated-orcid":false,"given":"Riccardo","family":"Dolcetti","sequence":"additional","affiliation":[{"name":"Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0518-8386","authenticated-orcid":false,"given":"Ranjeny","family":"Thomas","sequence":"additional","affiliation":[{"name":"Frazer Institute The University of Queensland  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3708"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18300"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800933"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12950-017-0159-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08476"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S477320"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9103323"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02186-6"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-025-01951-y"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202308131"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2313693120"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.201600013"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.08.026"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-21-0136"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba6098"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.90"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.04.003"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60644"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-02024-3"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2011.11.008"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34584"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-05-155176"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101176"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI96791"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.1c03243"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2024.05.003"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI195784"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000691"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201300078"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2017.11.007"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-17-0581"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.06.022"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9624"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad606"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1127896"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.70110","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cti2.70110","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.70110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:20:43Z","timestamp":1782278443000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.70110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":35,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/cti2.70110"],"URL":"https:\/\/doi.org\/10.1002\/cti2.70110","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"value":"2050-0068","type":"print"},{"value":"2050-0068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2025-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70110"}}