{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:16:59Z","timestamp":1792664219678,"version":"4.5.0"},"reference-count":38,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"unspecified","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE024550"],"award-info":[{"award-number":["R01DE024550"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2020,9,7]]},"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>CMP-001 is a novel Toll-like receptor-9 agonist that consists of an unmethylated CpG-A motif-rich G10 oligodeoxynucleotide (ODN) encapsulated in virus-like particles. <jats:italic>In situ<\/jats:italic> vaccination of CMP-001 is believed to activate local tumor-associated plasmacytoid dendritic cells (pDCs) leading to type I interferon secretion and tumor antigen presentation to T cells and systemic antitumor T cell responses. This study is designed to investigate if CMP-001 would enhance head and neck squamous cell carcinoma (HNSCC) tumor response to anti-programmed cell death protein-1 (anti-PD-1) therapy in a human papilloma virus-positive (HPV+) tumor mouse model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Immune cell activation in response to CMP-001\u00b1anti-Q\u03b2 was performed using co-cultures of peripheral blood mononuclear cells and HPV+\/HPV- HNSCC cells and then analyzed by flow cytometry. <jats:italic>In situ<\/jats:italic> vaccination with CMP-001 alone and in combination with anti-PD-1 was investigated in C57BL\/6 mice-bearing mEERL HNSCC tumors and analyzed for anti-Q\u03b2 development, antitumor response, survival and immune cell recruitment. The role of antitumor immune response due to CMP-001+anti-PD-1 treatment was investigated by the depletion of natural killer (NK), CD4<jats:sup>+<\/jats:sup> T, and CD8<jats:sup>+<\/jats:sup> T cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Results showed that the activity of CMP-001 on immune cell (pDCs, monocytes, CD4+\/CD8+ T cells and NK cells) activation depends on the presence of anti-Q\u03b2. A 2-week \u2018priming\u2019 period after subcutaneous administration of CMP-001 was required for robust anti-Q\u03b2 development in mice. <jats:italic>In situ<\/jats:italic> vaccination of CMP-001 was superior to unencapsulated G10 CpG-A ODN at suppressing both injected and uninjected (distant) tumors. <jats:italic>In situ<\/jats:italic> vaccination of CMP-001 in combination with anti-PD-1 therapy induced durable tumor regression at injected and distant tumors and significantly prolonged mouse survival compared with anti-PD-1 therapy alone. The antitumor effect of CMP-001+anti-PD-1 was accompanied by increased interferon gamma (IFN\u03b3)<jats:sup>+<\/jats:sup> CD4<jats:sup>+<\/jats:sup>\/CD8<jats:sup>+<\/jats:sup> T cells compared with control-treated mice. The therapeutic and abscopal effect of CMP-001+ anti-PD-1 therapy was completely abrogated by CD8<jats:sup>+<\/jats:sup> T cell depletion.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These results demonstrate that <jats:italic>in situ<\/jats:italic> vaccination with CMP-001 can induce both local and abscopal antitumor immune responses. Additionally, the antitumor efficacy of CMP-001 combined with \u03b1-PD-1 therapy warrants further study as a novel immunotherapeutic strategy for the treatment of HNSCC.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2020-000940","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T17:52:39Z","timestamp":1602784359000},"page":"e000940","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":58,"title":["<i>In situ<\/i> immunization of a TLR9 agonist virus-like particle enhances anti-PD1 therapy"],"prefix":"10.1136","volume":"8","clinical-trial-number":[{"clinical-trial-number":"nct02680184","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03618641","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Yinwen","family":"Cheng","sequence":"first","affiliation":[{"name":"Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa 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