{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:03:40Z","timestamp":1789607020059,"version":"build-2803163510"},"reference-count":33,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"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"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy Oncology"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.omton.2026.201334","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:08:00Z","timestamp":1788307680000},"page":"201334","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical evaluation of triple-mutated oncolytic herpes virus expressing fusion-type interleukin 12 for malignant melanoma"],"prefix":"10.1016","volume":"34","author":[{"given":"Miwako","family":"Iwai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Higuchi Nonaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Fukuhara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0523-8010","authenticated-orcid":false,"given":"Tomoki","family":"Todo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.omton.2026.201334_bib1","doi-asserted-by":"crossref","first-page":"4487","DOI":"10.1021\/acs.molpharmaceut.2c00775","article-title":"Options of Therapeutics and Novel Delivery Systems of Drugs for the Treatment of Melanoma","volume":"19","author":"Wang","year":"2022","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.omton.2026.201334_bib2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.3171\/2023.6.JNS23243","article-title":"Oncolytic viral therapy: a review and promising future directions","volume":"140","author":"Reddy","year":"2024","journal-title":"J. Neurosurg."},{"key":"10.1016\/j.omton.2026.201334_bib3","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1186\/s12935-024-03424-z","article-title":"Enhancing cancer therapy: the integration of oncolytic virus therapy with diverse treatments","volume":"24","author":"Yan","year":"2024","journal-title":"Cancer Cell Int."},{"key":"10.1016\/j.omton.2026.201334_bib4","doi-asserted-by":"crossref","first-page":"727","DOI":"10.3390\/vaccines13070727","article-title":"Advances in Oncolytic Viral Therapy in Melanoma: A Comprehensive Review","volume":"13","author":"Garg","year":"2025","journal-title":"Vaccines"},{"key":"10.1016\/j.omton.2026.201334_bib5","doi-asserted-by":"crossref","first-page":"916","DOI":"10.3390\/ph17070916","article-title":"Where Are We Now with Oncolytic Viruses in Melanoma and Nonmelanoma Skin Malignancies?","volume":"17","author":"Nassief","year":"2024","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.omton.2026.201334_bib6","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1200\/JCO.2014.58.3377","article-title":"Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma","volume":"33","author":"Andtbacka","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.omton.2026.201334_bib7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/14740338.2017.1274729","article-title":"The safety of talimogene laherparepvec for the treatment of advanced melanoma","volume":"16","author":"Gangi","year":"2016","journal-title":"Expert Opin. Drug Saf."},{"key":"10.1016\/j.omton.2026.201334_bib8","doi-asserted-by":"crossref","first-page":"6396","DOI":"10.1073\/pnas.101136398","article-title":"Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing","volume":"98","author":"Todo","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omton.2026.201334_bib9","doi-asserted-by":"crossref","first-page":"4119","DOI":"10.1038\/s41467-022-31262-y","article-title":"A phase I\/II study of triple-mutated oncolytic herpes virus G47\u0394 in patients with progressive glioblastoma","volume":"13","author":"Todo","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.omton.2026.201334_bib10","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1038\/s41591-022-01897-x","article-title":"Intratumoral oncolytic herpes virus G47\u0394 for residual or recurrent glioblastoma: a phase 2 trial","volume":"28","author":"Todo","year":"2022","journal-title":"Nat. Med."},{"key":"10.1016\/j.omton.2026.201334_bib11","first-page":"2541","article-title":"Effects of Single-Dose Interleukin-12 Exposure on Interleukin-12\u2013Associated Toxicity and Interferon-\u03b3 Production","volume":"90","author":"Leonard","year":"1997","journal-title":"Blood"},{"key":"10.1016\/j.omton.2026.201334_bib12","doi-asserted-by":"crossref","DOI":"10.1126\/science.270.5238.908.a","article-title":"IL-12 deaths: explanation and a puzzle","volume":"270","author":"Cohen","year":"1995","journal-title":"Science"},{"key":"10.1016\/j.omton.2026.201334_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2022.108189","article-title":"Novel strategies exploiting interleukin-12 in cancer immunotherapy","volume":"239","author":"Cirella","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.omton.2026.201334_bib14","doi-asserted-by":"crossref","first-page":"11548","DOI":"10.3390\/cimb46100686","article-title":"Interleukin-12 delivery strategies and advances in tumor immunotherapy","volume":"46","author":"Dong","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"10.1016\/j.omton.2026.201334_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.nantod.2024.102331","article-title":"Emerging IL-12-based nanomedicine for cancer therapy","volume":"57","author":"Xin","year":"2024","journal-title":"Nano Today"},{"key":"10.1016\/j.omton.2026.201334_bib16","doi-asserted-by":"crossref","first-page":"400","DOI":"10.3390\/cells9020400","article-title":"Oncolytic Virus Encoding a Master Pro-Inflammatory Cytokine Interleukin 12 in Cancer Immunotherapy","volume":"9","author":"Nguyen","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.omton.2026.201334_bib17","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1089\/10430340150218396","article-title":"Cytokine gene transfer enhances herpes oncolytic therapy in murine squamous cell carcinoma","volume":"12","author":"Wong","year":"2001","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omton.2026.201334_bib18","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-32353-x","article-title":"Enhanced Sensitivity of Patient-Derived Pediatric High-Grade Brain Tumor Xenografts to Oncolytic HSV-1 Virotherapy Correlates with Nectin-1 Expression","volume":"8","author":"Friedman","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.omton.2026.201334_bib19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/628697","article-title":"Preclinical Evaluation of Oncolytic \u0394\u03b3134.5 Herpes Simplex Virus Expressing Interleukin-12 for Therapy of Breast Cancer Brain Metastases","volume":"2012","author":"Cody","year":"2012","journal-title":"Int. J. Breast Cancer"},{"key":"10.1016\/j.omton.2026.201334_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbadis.2025.168033","article-title":"Engineered oncolytic herpes simplex virus expressing interleukin-12 suppresses tumorigenicity of hepatocellular carcinoma","volume":"1872","author":"Lv","year":"2026","journal-title":"Biochim. Biophys. Acta. Mol. Basis Dis."},{"key":"10.1016\/j.omton.2026.201334_bib21","first-page":"40","article-title":"Fusion peptide is superior to co-expressing subunits for arming oncolytic herpes virus with interleukin 12. Commun","volume":"3","author":"Fukuhara","year":"2023","journal-title":"Med. (Lond)"},{"key":"10.1016\/j.omton.2026.201334_bib22","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/258152a0","article-title":"Genetics of natural resistance to herpesvirus infections in mice","volume":"258","author":"Lopez","year":"1975","journal-title":"Nature"},{"key":"10.1016\/j.omton.2026.201334_bib23","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1111\/1523-1747.ep12295238","article-title":"Treatment of Experimental Subcutaneous Human Melanoma with a Replication-Restricted Herpes Simplex Virus Mutant","volume":"108","author":"Randazzo","year":"1997","journal-title":"J. Invest. Dermatol."},{"key":"10.1016\/j.omton.2026.201334_bib24","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/sj.gt.3301885","article-title":"ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties","volume":"10","author":"Liu","year":"2003","journal-title":"Gene Ther."},{"key":"10.1016\/j.omton.2026.201334_bib25","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s40425-019-0623-z","article-title":"Final analyses of OPTiM: a randomized phase III trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in unresectable stage III-IV melanoma","volume":"7","author":"Andtbacka","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.omton.2026.201334_bib26","article-title":"Antitumor power of oncolytic HSV engineered with IL-12 and IL-15","volume":"33","author":"Zhang","year":"2025","journal-title":"Mol. Ther. Oncol."},{"key":"10.1016\/j.omton.2026.201334_bib27","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.virs.2025.11.002","article-title":"Oncolytic HSV-1 expressing GM-CSF and IL-12 enhances anti-tumor efficacy in immunocompetent murine melanoma model","volume":"40","author":"Xiao","year":"2025","journal-title":"Virol. Sin."},{"key":"10.1016\/j.omton.2026.201334_bib28","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2020-000710","article-title":"Oncolytic vaccinia virus delivering tethered IL-12 enhances anti-tumor effects with improved safety","volume":"8","author":"Ge","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.omton.2026.201334_bib29","doi-asserted-by":"crossref","first-page":"3658","DOI":"10.1016\/j.ymthe.2022.06.010","article-title":"An armed oncolytic virus enhances the efficacy of tumor-infiltrating lymphocyte therapy by converting tumors to artificial antigen-presenting cells in situ","volume":"30","author":"Yang","year":"2022","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omton.2026.201334_bib30","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2022-006270","article-title":"Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase II trial","volume":"11","author":"Chesney","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.omton.2026.201334_bib31","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":"10.1016\/j.omton.2026.201334_bib32","article-title":"IL-12-mediated toxicity from localized oncolytic virotherapy can be reduced using systemic TNF blockade","volume":"32","author":"Valenzuela-Cardenas","year":"2024","journal-title":"Mol. Ther. Oncol."},{"key":"10.1016\/j.omton.2026.201334_bib33","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2018.1462431","article-title":"TumGrowth: An open-access web tool for the statistical analysis of tumor growth curves","volume":"7","author":"Enot","year":"2018","journal-title":"OncoImmunology"}],"container-title":["Molecular Therapy Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2950329926002109?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2950329926002109?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:08:44Z","timestamp":1789603724000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2950329926002109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["S2950329926002109"],"URL":"https:\/\/doi.org\/10.1016\/j.omton.2026.201334","relation":{},"ISSN":["2950-3299"],"issn-type":[{"value":"2950-3299","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Preclinical evaluation of triple-mutated oncolytic herpes virus expressing fusion-type interleukin 12 for malignant melanoma","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy Oncology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omton.2026.201334","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}],"article-number":"201334"}}