Enadenotucirev (previously known as ColoAd1) is a highly potent broad spectrum anti-cancer therapeutic currently in clinical development. Enadenotucirev is capable of selectively destroying tumor cells and at the same time attracting cells of the immune system. It is a non-naturally occurring Group B adenovirus developed using the principle of directed evolution to generate a virus with optimal anti-cancer properties. 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 is currently under investigation in clinical studies in the USA and Europe.
Unlike many “rationally” designed oncolytic viruses, which use recombinant techniques to modify wild type viruses with various insertions and deletions, PsiOxus has used the power of natural selection to generate an entirely novel virus, enadenotucirev , with optimized cancer-lytic properties. 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 elect 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.
Enadenotucirev is the lead virus that was discovered from this process. It is an Ad3 / Ad11p chimeric virus with optimized oncolytic characteristics. Initial clinical studies have established that it can be delivered intravenously and will reach and replicate in both primary and metastatic tumors.
View clinical trials with Enadenotucirev.
 Kuhn I, Harden P, Bauzon M, Chartier C, Nye J, Thorne S, Reid T, Ni S, Lieber A, Fisher K, Seymour L, Rubanyi GM, Harkins RN, Hermiston TW. Directed evolution generates a novel oncolytic virus for the treatment of colon cancer. PLoS ONE 2008; 3 (6):e2409.
 Di Y, Seymour L, Fisher K. Activity of a group B oncolytic adenovirus (ColoAd1) in whole human blood. Gene Therapy 2014; 21:440.
 Calvo E, Gil Martin M, Cubillo A, Machiels J, Rottey S, Mardjuadi F, Geboes K, Salazar R, Beadle J, Ellis C, Fisher K & Blanc C. A phase 1 study of enadenotucirev, an oncolytic Ad11/Ad3 chimeric group B adenovirus, administered intravenously – Analysis of dose expansion and repeat cycle cohorts in patients with metastatic colorectal cancer (mCRC). Ann Oncol 2014; 25 (suppl 4): iv367. [View poster presentation from ESMO 2014]
 Boni V, De La Portilla F, Cubillo A, Gil-Martin M, Calvo E, Salazar R, Santos C, Sanchez-Gastaldo A, Prados S, Sanjuan X, Bozada J.M, Duran H, Jurado M, Ellis C, Alvis S, Beadle J, Fisher K, Blanc C & Garcia-Carbonero R. A phase 1 mechanism of action study of intra-tumoural (IT) or intravenous (IV) administration of enadenotucirev, an oncolytic Ad11/Ad3 chimeric group B adenovirus in colon cancer patients undergoing resection of primary tumour. Ann Oncol 2014; 25 (suppl 4): iv368. [View poster presentation from ESMO 2014]
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 EnAd Mechanism of Action are currently the subject of on-going investigation.