COVID-19: Fighting viruses with viruses

Alan Parker and his team at an event in November 2019.

This entry is part 2 of 6 in the series COVID-19 research

COVID-19 is delaying cancer research and treatment. We’re catching up with some of the cancer researchers who are using their expertise, experience and equipment to help tackle COVID-19 and get cancer services back on track.

One lab thinks that the key is to fight the virus with another virus.

The main job of our immune system is to protect the body from potential threats – including viruses and cancer. In response to this, cancer cells have evolved multiple strategies to evade the immune system – allowing them to grow into larger and larger tumours.

At Cardiff University, Dr Alan Parker’s team looks at how we can pit one threat against another and use viruses to destroy cancer cells.

Building a Trojan Horse

The idea of giving a virus to someone with cancer may sound strange. But Parker’s team believe that, with a bit of fine-tuning, viruses can be trained to focus their destructive power on cancer cells.

The lab is particularly interested in a family of family of over 50 viruses, called adenoviruses. In most people, adenoviruses cause relatively mild conditions, such as an upset stomach or a cold (depending on the type of virus).

“We’re interested in how – at a molecular level – these viruses infect healthy cells and cause disease” says Parker. “By understanding how they do that, you can start to re-engineer the virus so it can hunt and destroy cancer cells.”

At its simplest, a virus is a bundle of genetic information wrapped up in an incredibly tiny shell. This protective coating is made up of proteins that allow the virus to interact with cells, infect them and then hijack the cell to create more of itself.

Through genetic engineering, Parker and his team modify the adenovirus DNA so that when the virus infects tumour cells, it makes them release antigens (proteins that the immune system uses to recognise and respond to threats) that are unique to the tumour.

This release teaches the immune system to be better able to target tumour cells and so – like a trojan horse – the cells inadvertantly cause their own destruction.

A battle of two viruses

It’s a technique the lab has been perfecting for several years, but their work was brought to a temporary halt by the COVID-19 outbreak.

The COVID-19 pandemic has forced universities to partially close, and a lot of Parker’s lab work had to be shut down.

Like many other scientists working at home, they wondered how they could use their skills to aid research into the virus.

After receiving a phone call from a colleague who wanted to develop tests to determine if people infected with COVID-19 had developed neutralising antibodies, Parker had a realisation – the technique his lab uses to help the immune system recognise cancer cells could also be used to train the immune system to recognise and destroy the COVID-19 virus.

“I was saying to the group, you know what might be more useful is if we engineer the adenovirus to express coronavirus antigens and use it like a vaccine.”

“It was a question of ‘who in the team was able to be sent in’ and ‘who was best placed to do the research’.”

Instead of being limited to tumour cells, the group are modifying adenovirus to enter as many cells as possible, using them as miniature factories to pump out coronavirus antigens.

This gives the immune system a chance to learn about what it can expect so when an actual COVID-19 infection occurs, the immune system is primed to deal with it.

While many labs around the world use adenoviruses as the basis for vaccines, Parker’s lab has one key advantage: freezers packed full of hundreds of adenoviruses, all subtly different.

This meant they could go back to some of the adenoviruses that they had discarded in the past as not being useful for targeting cancer and examine them in a new light.

“We know we’ve got adenoviruses that are good at what they do. Instead of expressing a cancer antigens to help the immune system recognise and kill cancer cells, we’re just going to change the tumour antigen for a viral antigen and try and make the body recognise and eliminate coronavirus when it enters the body.”

“Mouse is a very limited model…you can’t give mice [COVID-19] and see if the vaccine is protective because [COVID-19] doesn’t infect mice.”

“We think – based on timelines of other things we’ve produced – it will take us around two months to be able to produce our first batches of research grade vaccines for evaluation.”

It’s an exciting timeframe, but for a lab whittled down to just 4 researchers, this is just the start of the process of developing any kind of usable vaccine.

One of the pivotal moments will be injecting mice with their modified adenoviruses and seeing if the immune system can respond in a way that indicates it’s primed to fight off the COVID-19 virus. But there’s one big issue – mice can’t be infected by COVID-19. This means the team can’t test out whether the immune responses developed in mice will actually protect against the virus. Parker knows that the next step requires even more collaboration.

“I feel my role here is to make the tools and do what we can reasonably do in the in the fastest time possible, and then hand it over to the experts,” says Parker.

Coming back to cancer

“Cancer immunotherapies have spun out of basic and fundamental findings in immunology, and often the immunology of infectious diseases. So actually the two things are very much intertwined.”

Although they might seem like two separate worlds, Parker think that this work into COVID-19 will allow them to get a better understanding of their own research and how adenoviruses can be optimised as treatments for cancer.

“We will take that knowledge into the cancer setting to look at how the body can respond when you provide a tumour antigen in the same way, and how it can then mount an anti-cancer response. So it all kind of feeds together – at least in my head, it does.”

Alex

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