Enadenotucirev (previously known as ColoAd1) is a clinical stage, highly potent broad spectrum oncolytic virus therapeutic with the potential to target the vast majority of solid tumors. Efficient intravenous delivery of enadenotucirev has been demonstrated clinically, giving it the potential to offer systemic therapy for advanced cancers.
Enadenotucirev is currently under investigation in clinical studies in the USA and Europe, including a collaboration with Bristol-Myers Squibb on the combination with Opdivo® in multiple tumor cohorts.
Enadenotucirev is a non-naturally occurring Group B adenovirus developed using the principle of directed evolution to generate a virus with optimal anti-cancer properties including intravenous delivery. In particular, enadenotucirev was selected due to its ability to retain cancer killing activity in the presence of fresh human blood and thus be available as an intravenously administered product. Enadenotucirev replicates only in tumor tissue and not within normal, non-cancerous tissue and is therefore anticipated to be capable of selectively destroying tumor cells and at the same time attracting cells of the immune system. This patent protected process of directed evolution is summarized below and in Figure 1.
- Firstly, a chimeric adenovirus library was created by homologous recombination under atypical conditions of super-infection.
- Multiple rounds of selection then identified those chimeric viruses with a tumour dependent phenotype that also rapidly killed tumor cells.
- The most potent oncolytic viruses were then screened on normal cells to select one with a very high therapeutic index.
- Finally, the potency of the lead candidates was assessed in the presence of fresh human blood to determine which viruses had the potential to retain their oncolytic potency after intravenous dosing.
Clinical studies have established that enadenotucirev can be delivered intravenously and will reach and replicate in both primary and metastatic tumors. Enadenotucirev forms the basis of our next generation oncolytic gene therapy virus platform, Tumor-Specific Immuno-Gene Therapy (T-SIGn).
View clinical trials with Enadenotucirev.
Figure 1. – Enadenotucirev: Developed using directed evolution
Enadenotucirev: Mechanism of Action
A summary animation illustrating how enadenotucirev (termed ColoAd1 in this video) targets cancer cells. Please note, the exact details surrounding the enadenotucirev Mechanism of Action are currently the subject of on-going investigation.