Oncolytic virotherapy, using viruses such as vesicular stomatitis virus (VSVΔ51) and Herpes Simplex Virus-1 (HSV-1) to selectively attack cancer cells, faces challenges such as cellular resistance mediated by the interferon (IFN) response. 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 VSVΔ51 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 VSVΔ51 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\'s 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\'s 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\'s 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.

UNASSIGNED: Safe, effective, long-term oral therapies are needed for plaque psoriasis. This study aimed to assess the safety and effectiveness of tepilamide fumarate (a fumaric acid ester) extended-release tablets.
UNASSIGNED: This Phase IIb, randomized, double-blind, placebo-controlled, 24-week, multicenter study treated adults with moderate-to-severe plaque psoriasis with tepilamide fumarate 400 mg once (QD) or twice daily (BID), 600 mg BID, or placebo. Coprimary endpoints were the proportion of patients achieving ≥75% reduction in the Psoriasis Area and Severity Index (PASI-75) and Investigator\'s Global Assessment (IGA) of clear or almost clear (≥2 points\' reduction).
UNASSIGNED: A total of 426 patients were randomized (mean age 49.6 [±13.0] years). There was a ≥75% PASI reduction in 39.7%, 47.2%, 44.3%, and 20.0% in the 400 mg QD, 400 mg BID, 600 mg BID, and placebo groups, respectively; IGA treatment success was 35.7%, 41.4%, 44.4%, and 22.0%, respectively. Between 50%-66% of tepilamide fumarate and 48% of placebo patients experienced ≥1 treatment-emergent adverse event. Gastrointestinal intolerance (20%-42%), infection (6%-18%), and decreased lymphocyte count (4%-9%) were more common with tepilamide fumarate.
UNASSIGNED: High placebo response somewhat limits the utility of these findings.
UNASSIGNED: Patients with moderate-to-severe plaque psoriasis treated with oral tepilamide fumarate demonstrated positive response.