{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T19:48:51Z","timestamp":1782935331389,"version":"3.54.5"},"reference-count":36,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"unspecified","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,3,27]]},"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1)\/programmed cell death ligand 1 (PD-L1) have demonstrated clinical efficacy in advanced melanoma, but only a subset of patients with inflamed tumors are responsive. Talimogene laherparepvec (T-VEC), a modified herpes simplex virus type 1 (HSV-1) expressing granulocyte-macrophage colony-stimulating factor (GM-CSF), is a first-in-class oncolytic immunotherapy approved for the treatment of melanoma and has been shown to inflame the tumor microenvironment. To evaluate the potential and mechanisms of T-VEC to elicit systemic antitumor immunity and overcome resistance to checkpoint inhibitors in murine tumor models, OncoVEX<jats:sup>mGM-CSF<\/jats:sup> was developed similarly to T-VEC, except the human GM-CSF transgene was replaced with murine GM-CSF. Previous work had demonstrated that OncoVEX<jats:sup>mGM-CSF<\/jats:sup> generated systemic antitumor immunity dependent on CD8+ T cells in an immune checkpoint-sensitive tumor cell model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A novel B16F10 syngeneic tumor model with both HSV-1\u2212permissive subcutaneous tumors and HSV-1\u2212refractory experimental lung metastasis was used to study the local and systemic effects of OncoVEX<jats:sup>mGM-CSF<\/jats:sup> treatment alone or in combination with checkpoint inhibitors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Intratumoral injection of OncoVEX<jats:sup>mGM-CSF<\/jats:sup> in combination with an anti-CTLA-4 or anti-PD-1 blocking antibody led to increased tumor growth inhibition, a reduction in the number of lung metastases, and prolonged animal survival. OncoVEX<jats:sup>mGM-CSF<\/jats:sup> induced both neoantigen-specific and tumor antigen-specific T-cell responses. Furthermore, cured mice from the combination treatment of OncoVEX<jats:sup>mGM-CSF<\/jats:sup> and anti-CTLA-4 antibody rejected tumor rechallenges.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These data support the concept that T-VEC and checkpoint inhibition may be an effective combination to treat patients with advanced melanoma.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2022-006374","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T12:52:01Z","timestamp":1683723121000},"page":"e006374","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["OncoVEX<sup>mGM-CSF<\/sup>expands tumor antigen-specific CD8+ T-cell response in preclinical models"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct02263508","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02263508","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Juan","family":"Estrada","sequence":"first","affiliation":[{"name":"Amgen Inc, Thousand Oaks, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghui","family":"Zhan","sequence":"additional","affiliation":[{"name":"Amgen Inc, Thousand Oaks, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petia","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Amgen Inc, Thousand Oaks, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Werner","sequence":"additional","affiliation":[{"name":"Amgen Inc, Thousand Oaks, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro J","family":"Beltran","sequence":"additional","affiliation":[{"name":"BridgeBio Pharma, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"DeVoss","sequence":"additional","affiliation":[{"name":"Amgen Inc, Thousand Oaks, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Qing","sequence":"additional","affiliation":[{"name":"BeiGene, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keegan S","family":"Cooke","sequence":"additional","affiliation":[{"name":"Amgen Inc, Thousand Oaks, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"key":"2025100302091790000_11.5.e006374.1","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1007\/s00262-017-2025-8","article-title":"Oncolytic immunotherapy: unlocking the potential of viruses to help target cancer","volume":"66","author":"Hamid","year":"2017","journal-title":"Cancer Immunol Immunother"},{"key":"2025100302091790000_11.5.e006374.2","unstructured":"IMLYGIC\u00ae . Talimogene laherparepvec. Thousand Oaks, CA: Amgen Inc, 2017."},{"key":"2025100302091790000_11.5.e006374.3","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301885"},{"key":"2025100302091790000_11.5.e006374.4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.21.11307"},{"key":"2025100302091790000_11.5.e006374.5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005449","article-title":"The herpes simplex virus neurovirulence factor \u03b334.5: revealing virus-host interactions","volume":"12","author":"Wilcox","year":"2016","journal-title":"PLoS Pathog"},{"key":"2025100302091790000_11.5.e006374.6","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-016-5286-0"},{"key":"2025100302091790000_11.5.e006374.7","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar4060"},{"key":"2025100302091790000_11.5.e006374.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.03.001"},{"key":"2025100302091790000_11.5.e006374.9","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-0367"},{"key":"2025100302091790000_11.5.e006374.10","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160801"},{"key":"2025100302091790000_11.5.e006374.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5256.1734"},{"key":"2025100302091790000_11.5.e006374.12","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12030738","article-title":"Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence","volume":"12","author":"Vaddepally","year":"2020","journal-title":"Cancers (Basel)"},{"key":"2025100302091790000_11.5.e006374.13","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)01206-X"},{"key":"2025100302091790000_11.5.e006374.14","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/s41571-021-00473-5","article-title":"PD-L1 as a biomarker of response to immune-checkpoint inhibitors","volume":"18","author":"Doroshow","year":"2021","journal-title":"Nat Rev Clin Oncol"},{"key":"2025100302091790000_11.5.e006374.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.12.011"},{"key":"2025100302091790000_11.5.e006374.16","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-0681"},{"key":"2025100302091790000_11.5.e006374.17","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.73.7379"},{"key":"2025100302091790000_11.5.e006374.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.08.027"},{"key":"2025100302091790000_11.5.e006374.19","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1200\/JCO.22.00343","article-title":"Randomized, double-blind, placebo-controlled, global phase III trial of talimogene laherparepvec combined with pembrolizumab for advanced melanoma","volume":"41","author":"Chesney","year":"2023","journal-title":"J Clin Oncol"},{"key":"2025100302091790000_11.5.e006374.20","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(19)30388-2"},{"key":"2025100302091790000_11.5.e006374.21","doi-asserted-by":"crossref","first-page":"9518","DOI":"10.1200\/JCO.2022.40.16_suppl.9518","article-title":"Primary analysis of a phase 2, open-label, multicenter trial of talimogene laherparepvec (T-VEC) plus pembrolizumab (pembro) for the treatment (tx) of patients (pts) with advanced melanoma (MEL) who progressed on prior anti\u2013PD-1 therapy: MASTERKEY-115","volume":"40(16_Suppl)","author":"Gastman","year":"2022","journal-title":"J Clin Oncol"},{"key":"2025100302091790000_11.5.e006374.22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15229-5"},{"key":"2025100302091790000_11.5.e006374.23","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-021-00389-3"},{"key":"2025100302091790000_11.5.e006374.24","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ebiom.2019.10.032","article-title":"Oncolytic newcastle disease virus expressing a checkpoint inhibitor as a radioenhancing agent for murine melanoma","volume":"49","author":"Vijayakumar","year":"2019","journal-title":"EBioMedicine"},{"key":"2025100302091790000_11.5.e006374.25","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1080\/14712598.2020.1729351","article-title":"Combination therapy with oncolytic viruses and immune checkpoint inhibitors","volume":"20","author":"Chiu","year":"2020","journal-title":"Expert Opin Biol Ther"},{"key":"2025100302091790000_11.5.e006374.26","unstructured":"National Research Council . Guide for the care and use of laboratory animals. Eighth edition. Washington, DC: The National Academies Press, 2011: 246."},{"key":"2025100302091790000_11.5.e006374.27","doi-asserted-by":"publisher","DOI":"10.1097\/00002371-200003000-00001"},{"key":"2025100302091790000_11.5.e006374.28","first-page":"7920","article-title":"Immunization against endogenous retroviral tumor-associated antigens","volume":"61","author":"Kershaw","year":"2001","journal-title":"Cancer Res"},{"key":"2025100302091790000_11.5.e006374.29","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.3.453"},{"key":"2025100302091790000_11.5.e006374.30","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.2.897"},{"key":"2025100302091790000_11.5.e006374.31","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0206223","article-title":"Tumor-immune profiling of murine syngeneic tumor models as a framework to guide mechanistic studies and predict therapy response in distinct tumor microenvironments","volume":"13","author":"Yu","year":"2018","journal-title":"PLoS One"},{"key":"2025100302091790000_11.5.e006374.32","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-3289"},{"key":"2025100302091790000_11.5.e006374.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.052"},{"key":"2025100302091790000_11.5.e006374.34","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-1825"},{"key":"2025100302091790000_11.5.e006374.35","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-017-00627-z","article-title":"Checkpoint blockade immunotherapy reshapes the high-dimensional phenotypic heterogeneity of murine intratumoural neoantigen-specific CD8+ T cells","volume":"8","author":"Fehlings","year":"2017","journal-title":"Nat Commun"},{"key":"2025100302091790000_11.5.e006374.36","doi-asserted-by":"publisher","DOI":"10.1038\/nature19330"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2022-006374","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T09:09:24Z","timestamp":1759482564000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2022-006374"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5]]},"references-count":36,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5,10]]},"published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1136\/jitc-2022-006374"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2022-006374","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5]]}}}