Scientific Publications Database
Article Title: Dimethyl fumarate potentiates oncolytic virotherapy through NF-kappa B inhibitionAuthors: Selman, Mohammed; Ou, Paula; Rousso, Christopher; Bergeron, Anabel; Krishnan, Ramya; Pikor, Larissa; Chen, Andrew; Keller, Brian A.; Ilkow, Carolina; Bell, John C.; Diallo, Jean-Simon
Journal: SCIENCE TRANSLATIONAL MEDICINE Volume 10 Issue 425
Date of Publication:2018
Abstract:
Resistance to oncolytic virotherapy is frequently associated with failure of tumor cells to get infected by the virus. Dimethyl fumarate (DMF), a common treatment for psoriasis and multiple sclerosis, also has anticancer properties. We show that DMF and various fumaric and maleic acid esters (FMAEs) enhance viral infection of cancer cell lines as well as human tumor biopsies with several oncolytic viruses (OVs), improving therapeutic outcomes in resistant syngeneic and xenograft tumor models. This results in durable responses, even in models otherwise refractory to OV and drug monotherapies. The ability of DMF to enhance viral spread results from its ability to inhibit type I interferon (IFN) production and response, which is associated with its blockade of nuclear translocation of the transcription factor nuclear factor kappa B (NF-kappa B). This study demonstrates that unconventional application of U.S. Food and Drug Administration-approved drugs and biological agents can result in improved anticancer therapeutic outcomes.