{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:32:41Z","timestamp":1792801961706,"version":"4.5.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:00:00Z","timestamp":1701993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["12837"],"award-info":[{"award-number":["12837"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"International Joint Usage\/Research Center, the Institute of Medical Science, the University of Tokyo","award":["2019-K3010"],"award-info":[{"award-number":["2019-K3010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Immune checkpoint blockade (ICB) immunotherapies have emerged as promising strategies for the treatment of cancer; however, there remains a need to improve their efficacy. Determinants of ICB efficacy are the frequency of tumor mutations, the associated neoantigens, and the T cell response against them. Therefore, it is expected that neoantigen vaccinations that boost the antitumor T cell response would improve ICB therapy efficacy. The aim of this study was to develop a highly immunogenic vaccine using pattern recognition receptor agonists in combination with synthetic long peptides to induce potent neoantigen-specific T cell responses. We determined that the combination of the TLR9 agonist K-type CpG oligodeoxynucleotides (K3 CpG) with the STING agonist c-di-AMP (K3\/c-di-AMP combination) significantly increased dendritic cell activation. We found that immunizing mice with 20-mer of either an OVA peptide, low-affinity OVA peptides, or neopeptides identified from mouse melanoma or lung mesothelioma, together with K3\/c-di-AMP, induced potent Ag-specific T cell responses. The combined K3\/c-di-AMP adjuvant formulation induced 10 times higher T cell responses against neopeptides than the TLR3 agonist polyinosinic:polycytidylic acid, a derivative of which is the leading adjuvant in clinical trials of neoantigen peptide vaccines. Moreover, we demonstrated that our K3\/c-di-AMP vaccine formulation with 20-mer OVA peptide was capable of controlling tumor growth and improving survival in B16-F10-OVA tumor-bearing C57BL\/6 mice and synergized with anti-PD-1 treatment. Together, our findings demonstrate that the K3\/c-di-AMP vaccine formulation induces potent T cell immunity against synthetic long peptides and is a promising candidate to improve neoantigen vaccine platform.<\/jats:p>","DOI":"10.4049\/jimmunol.2300038","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T14:39:00Z","timestamp":1702046340000},"page":"455-465","source":"Crossref","is-referenced-by-count":19,"title":["TLR9 plus STING Agonist Adjuvant Combination Induces Potent Neopeptide T Cell Immunity and Improves Immune Checkpoint Blockade Efficacy in a Tumor Model"],"prefix":"10.1093","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-8937","authenticated-orcid":false,"given":"Melisa D","family":"Castro Eiro","sequence":"first","affiliation":[{"name":"Department of Immunology; Erasmus University Medical Center , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4945-1032","authenticated-orcid":false,"given":"Kou","family":"Hioki","sequence":"additional","affiliation":[{"name":"Department of Immunology; Erasmus University Medical Center , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5124-9228","authenticated-orcid":false,"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology; Erasmus University Medical Center , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merel E P","family":"Wilmsen","sequence":"additional","affiliation":[{"name":"Department of Immunology; Erasmus University Medical Center , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caoimhe H","family":"Kiernan","sequence":"additional","affiliation":[{"name":"Department of Immunology; Erasmus University Medical Center , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4492-446X","authenticated-orcid":false,"given":"Inge","family":"Brouwers-Haspels","sequence":"additional","affiliation":[{"name":"Department of Immunology; Erasmus University Medical Center , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8773-2543","authenticated-orcid":false,"given":"Marjan","family":"van Meurs","sequence":"additional","affiliation":[{"name":"Department of Immunology; Erasmus University Medical Center , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9410-035X","authenticated-orcid":false,"given":"Manzhi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Immunology; Erasmus University Medical Center , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harm","family":"de Wit","sequence":"additional","affiliation":[{"name":"Department of Immunology; Erasmus University Medical Center , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4169-9888","authenticated-orcid":false,"given":"Dwin G B","family":"Grashof","sequence":"additional","affiliation":[{"name":"Department of Immunology; Erasmus University Medical Center , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9794-1477","authenticated-orcid":false,"given":"Harmen J G","family":"van de Werken","sequence":"additional","affiliation":[{"name":"Department of Immunology; Erasmus University Medical Center , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4654-7509","authenticated-orcid":false,"given":"Yvonne M","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Immunology; Erasmus University Medical Center , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-8620","authenticated-orcid":false,"given":"Christopher","family":"Schliehe","sequence":"additional","affiliation":[{"name":"Department of Immunology; Erasmus University Medical Center , Rotterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5189-3529","authenticated-orcid":false,"given":"Burcu","family":"Temizoz","sequence":"additional","affiliation":[{"name":"Division of Vaccine Science, Department of Microbiology and Immunology, International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouji","family":"Kobiyama","sequence":"additional","affiliation":[{"name":"Division of Vaccine Science, Department of Microbiology and Immunology, International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6728-3872","authenticated-orcid":false,"given":"Ken J","family":"Ishii","sequence":"additional","affiliation":[{"name":"Division of Vaccine Science, Department of Microbiology and Immunology, International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7690-5218","authenticated-orcid":false,"given":"Peter D","family":"Katsikis","sequence":"additional","affiliation":[{"name":"Department of Immunology; 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