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).
Dr Alan Parker is a BSGCT Board member. In this role he chairs the Professional Collaboration sub-committee, and vice chair of the communication and promotion sub-committee, and chaired the 2017 annual meeting in Cardiff. Alan is actively involved in a wide range of public engagement activities, both within his role with BSGCT and in promoting the work of the lab locally, and is a registered STEM ambassador.
|Area of research||Members|
|Vectorology||Richard Stanton (Cardiff University)|
Gavin Wilkinson (Cardiff University)
Lynda Coughlan (Icahn School of Medicine, New York)
|Oncolytic adenoviruses||Gunnel Hallden (Barts Cancer Institute)|
Robert Carlisle (Oxford University)
Len Seymour (Oxford University)
Richard Vile (Mayo Institute, Rochester, USA)
|αvβ6 biology||John Marshall (Bart’s Cancer Institute)|
|Structural studies of viral proteins||Pierre Rizkallah (Cardiff University)|
Alex Greenshields-Watson (Cardiff University)
|Translational immunology||Awen Gallimore (Cardiff University)|
Andy Godkin (Cardiff University)
|Advanced therapeutics for breast cancer||Richard Clarkson (Cardiff University)|
Luke Piggott (Cardiff University)
|Advanced therapeutics for pancreatic cancer||Gunnel Hallden (Bart’s Cancer Institute)|
Catherine Hogan (Cardiff University)
|Translational studies||John Chester (Cardiff University)|
|Ovarian cancer collaborators||Rachel Jones (Cardiff University)|
Emma Hudson (Cardiff University)
Louise Hanna (Cardiff University)
James Cronin (Cardiff University)
Steve Conlan (Swansea)
|Viral proteins as drug delivery agents||Angela Casini (Cardiff University)|
Steven Paisey (Cardiff University)