Oncolytic Adenovirus Virology

Research within the Oncolytic Adenovirus Virology lab is focused on developing bespoke oncolytic adenoviral vectors for translational cancer applications.

To achieve this, we are developing tumour selective virotherapies that selectively infect cancer cells, leaving normal cells uninfected. To achieve this, we take two approaches. Our first approach is a “bottom up” approach involving the use of Ad5, a well described, well understood and clinically well studied virus. Although safe, Ad5 has a number of features which limits efficacy as a tumour selective virotherapy.

Firstly, the primary Ad5 receptor, hCAR (human coxsackie and adenovirus receptor) is ubiquitously expressed on red blood cells and in all tissues, located at tight junctions, but is commonly downregulated or even absent in advanced cancers, and therefore represents a poor target for tumour targeting strategies.

Secondly, uptake into immune cells, mediated by the interaction between αvβ3/5 integrin and the Ad5 penton base protein can promote significant dose limiting toxicities. Finally, intravascular delivery of Ad5, a pre-requisite for therapy of metastatic disease, is compromised for Ad5 due to the high affinity interaction with the blood clotting factor, FX, which bridges the virus: FX complex to HSPGs and is responsible for the significant levels of hepatic uptake of Ad5 based virotherapies (overviewed in Figure.1).

To target the refined, basal vector to tumour cells, we further modulate the vector to incorporate peptide ligands binding to tumour specific markers, such as αvβ6 integrin (Figure.2).

Discover more about the research carried out into Infection and Immunity.