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Oct 2018 - Oct 2022

In situ evolution of cancer binding oligopeptides for targeted virotherapy applications

Student

Tabitha Cunliffe

Location

Cardiff

Funding Amount

£12,750

Supervisor

Dr Alan Parker

Cancer Type

All

Funding Type

PhD

Status

Complete

Research Type

Treatment

This PhD is part funded through the Knowledge and Economy Skills Scholarship 2 Programme which you can find out more about here

Using viruses to treat cancer (also known as “virotherapy”) may seem illogical, but it has important advantages compared to conventional anti-cancer therapies. A major benefit lies in the ability of the therapeutic to amplify itself within a cancer following successful infection of tumour cells - a feature unique to biological agents. In doing so, infected cancer cells produce millions more copies of virus, before bursting (“lysing”) the infected cancer cell and spreading the daughter virions to surrounding cells, to repeat the process. This “lytic” activity also helps to stimulate the host immune system, helping it to recognise and destroy the cancerous cells. Unfortunately, viruses have not evolved to selectively recognise cancerous cells, and thus, in their “untrained” state are unable to distinguish between malignant and healthy cells. To be useful anti-cancer agents, it is critical that viruses are “trained” to discriminate between transformed, cancerous cells and healthy cells. To achieve this requires a solution to two equally fundamental problems. Firstly there is a need to understand at the molecular level how the virus infects “normal cells” and makes us ill, and modify the virus to prevent it using these preferred mechanisms. Secondly, the virus needs to be modified so that it can recognise and infect cancerous cells using “markers” on cancer cells that make them stand out as different. Previously good progress has been made on the first of these areas, and produced a “basal” virus that is unable to infect healthy cells. In this project, a new technology will be established, with experts based at Warwick University (Alfonso Jarmillo) to allow the “training” of individual virus proteins to recognise and bind to markers on cancer cells, enabling the generation of bespoke virotherapies that can seek out and destroy cancer cells.

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