David Olagnier

David Olagnier

An engineered virus to combat cancer

One of the cancer therapies currently under development aims, to put it simply, to fight cancer cells using a genetically modified virus – an oncolytic virus – which acts as a “precision missile”.

The genetically modified virus particles target the cancer cells, then penetrate and destroy them – without causing any damage to healthy tissue.

‘In the long term, this method has great potential for developing therapies which can be applied to the many types of cancer cell line that are highly resistant to both chemotherapy and radiation treatment,’ says David Olagnier from the Department of Biomedicine at Aarhus University.

David Olagnier holds a PhD in immunology and infectious diseases, and he is one of the nine exceptionally talented researchers who have been named 2020 Lundbeck Foundation Fellows. With the help of the accompanying grant, he can now establish his own research group at the Department of Biomedicine.

This group will spend the next five years researching oncolytic-virus treatment of cancer, focusing on prostate cancer and lung cancer. They will initially conduct cell trials and then studies on mice, and it is hoped that the results will be so promising that the therapy can eventually be offered to patients.

David Olagnier and his colleagues will study a specific protein – Nrf2 – which belongs to the group of transcription factors. This means that the protein helps ensure correct expression of a range of genes – or, in simpler terms, ‘that the right DNA buttons are pushed at the right time’.

The reason why this protein is so interesting in relation to cancer is that an increasing number of scientific studies indicate that Nrf2 could be a major factor in cancer cells’ resistance to, among other things, chemotherapy and radiation treatment. David Olagnier explains:

‘The problem arises when gene expression is dysfunctional. In such situations, cancer cells have particularly favourable conditions for growth – and the body’s immune system, which in theory should be able to combat the sick cells, can’t cope. And this particular type of tumour is not only tough, it’s highly resistant to chemotherapy and radiation treatment.’

But how is a bespoke virus suitable for combating this type of tumour? One of the reasons is that cancer cells are usually weak when it comes to resisting viral attacks. Their defences against the virus are full of holes. A genetically engineered virus is therefore able to penetrate the cancer cells but not the healthy ones, which will reject this “precision missile”.

In addition, once the genetically engineered virus has entered the cancer cells, it can produce molecules which strengthen the body’s own immune system and, ultimately, kill the cancer cells by causing them to burst.

There is currently only one approved cancer therapy based on oncolytic virus. It is used in the USA for treating a particular type of skin cancer. The virus that David Olagnier will attempt to transform into a “precision missile” using genetic engineering is known as vesicular stomatitis virus (VSV). It infects cattle and pigs but is harmless to human beings.