ICOVIR-5

ICOVIR-5 is an optimized oncolytic adenovirus designed for cancer treatment. It combines several genetic modifications to enhance tumor selectivity while maintaining potent anti-tumor activity. ## Mechanism of Action ICOVIR-5 (also known as Ad-DM-E2F-K-Delta24RGD) works through a dual mechanism: 1. **Selective Replication in Cancer Cells**: ICOVIR-5 contains E1a transcriptional control by an insulated form of the E2F promoter combined with the Delta24 mutation of E1a. This design targets cells with a deregulated E2F-RB pathway, which is common in tumor cells[3][5]. 2. **Enhanced Tumor Cell Entry**: The virus incorporates the RGD modification in the fiber protein, which improves its ability to infect tumor cells[5][6]. ## Clinical Development ICOVIR-5 has been evaluated in clinical trials: - It has been tested in a first-in-human, dose-escalation phase I clinical trial as a single intravenous infusion in patients with advanced malignant melanoma (ClinicalTrials.gov: NCT01864759)[4]. - The recommended phase II dose was established at 3.3 × 10^12 viral particles after dose-limiting hepatic toxicity (transaminitis) was observed at higher doses[4]. - It has also been used in combination with mesenchymal stem cells (MSCs) in a therapy called "Celyvir" for treating pediatric and adult patients with solid tumors[4][10]. ## Clinical Outcomes - In clinical trials, two pediatric patients with neuroblastoma showed disease stabilization when treated with Celyvir (MSCs infected with ICOVIR-5)[4]. - When used in combination with mesenchymal stem cells, ICOVIR-5 has shown enhanced antitumor efficacy associated with higher tumor infiltration of CD8+ and CD4+ T lymphocytes, suggesting immune system involvement in its therapeutic effect[10]. ## Manufacturing The clinical batch of ICOVIR-5 was manufactured at the Center for Cell and Gene Therapy at Baylor College of Medicine (Houston, TX) under good manufacturing practices (GMP) conditions using A549 cells[6]. ICOVIR-5 represents an innovative approach to cancer treatment through selective oncolytic virus therapy, with ongoing research exploring its potential in various cancer types.

Other names

Ad-DM-E2F-K-Δ24RGD