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Dimethyl fumarate (DMF) is used in the treatment of multiple sclerosis and psoriasis and is recognized for its anti-cancer properties and has been shown to enhance both VSV\u039451 and HSV-1 oncolytic activity. Tepilamide fumarate (TPF) is a DMF analog currently undergoing clinical trials for the treatment of moderate-to-severe plaque psoriasis. The aim of this study was to evaluate the potential of TPF in enhancing the effectiveness of oncolytic viruses. In vitro, TPF treatment rendered 786-0 carcinoma cells more susceptible to VSV\u039451 infection, leading to increased viral replication. It outperformed DMF in both increasing viral infection and increasing the killing of these resistant cancer cells and other cancer cell lines tested. Ex vivo studies demonstrated TPF\u2019s selective boosting of oncolytic virus infection in cancer cells without affecting healthy tissues. Effectiveness was notably high in pancreatic and ovarian tumor samples. Our study further indicates that TPF can downregulate the IFN pathway through a similar mechanism to DMF, making resistant cancer cells more vulnerable to viral infection. Furthermore, TPF\u2019s impact on gene therapy was assessed, revealing its ability to enhance the transduction efficiency of vectors such as lentivirus, adenovirus type 5, and adeno-associated virus type 2 across various cell lines. This data underscore TPF\u2019s potential role in not only oncolytic virotherapy but also in the broader application of gene therapy. Collectively, these findings position TPF as a promising agent in oncolytic virotherapy, warranting further exploration of its therapeutic potential.<\/jats:p>","DOI":"10.3390\/v16060920","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T11:50:09Z","timestamp":1717588209000},"page":"920","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tepilamide Fumarate as a Novel Potentiator of Virus-Based Therapy"],"prefix":"10.3390","volume":"16","author":[{"given":"Akram","family":"Alwithenani","sequence":"first","affiliation":[{"name":"Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada"},{"name":"Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Department of Clinical Laboratory Science, Faculty of Applied Medical Science, Umm Al-Qura University, Makkah 24382, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rozanne","family":"Arulanandam","sequence":"additional","affiliation":[{"name":"Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9407-4315","authenticated-orcid":false,"given":"Boaz","family":"Wong","sequence":"additional","affiliation":[{"name":"Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada"},{"name":"Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus M.","family":"Spinelli","sequence":"additional","affiliation":[{"name":"Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Chen","sequence":"additional","affiliation":[{"name":"Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glib","family":"Maznyi","sequence":"additional","affiliation":[{"name":"Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria H.","family":"Gilchrist","sequence":"additional","affiliation":[{"name":"Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada"},{"name":"Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Apoptosis Research Center, Ottawa, ON K1H 8L1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0396-9138","authenticated-orcid":false,"given":"Tommy","family":"Alain","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"},{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Apoptosis Research Center, Ottawa, ON K1H 8L1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Simon","family":"Diallo","sequence":"additional","affiliation":[{"name":"Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada"},{"name":"Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,5]]},"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/6\/920\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:54:18Z","timestamp":1760108058000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/6\/920"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,5]]},"references-count":0,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["v16060920"],"URL":"https:\/\/doi.org\/10.3390\/v16060920","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,5]]}}}