Viruses may boost immunotherapy in brain and breast cancer

Cancer Research UK

Infecting tumours with viruses may boost the success of immunotherapy for brain and breast cancers, according to two new studies. 

Immunotherapy treatments can trigger impressive responses in patients with a handful of advanced cancers. But success has been limited in both brain and breast cancers.

"When you infect a cancer cell with a virus, it raises a big red flag, which helps the immune system recognise and attack the cancer."Professor John Bell, University of Ottawa

The new studies, both published in Science Translational Medicine, suggest that cancer-targeting viruses could prime these tumours for subsequent immune attack.

Professor Alan Melcher, an expert in using viruses to treat cancer at The Institute of Cancer Research, London (ICR), and senior author on the brain tumour study, said that the findings pave the way for further clinical testing. 

“Our immune systems aren't very good at 'seeing' cancers -- partly because cancer cells look like our body's own cells, and partly because cancers are good at telling immune cells to turn a blind eye,” he said. “But the immune system is very good at seeing viruses.” 

The first study, led by researchers at the University of Leeds and the ICR, included a small number of patients with either an advanced type of brain tumour, called high grade glioma, or with another type of cancer that had spread to the brain. 

The scientists, part-funded by Cancer Research UK, injected 9 patients with a virus that seeks out cancer cells. The patients then underwent surgery to remove their tumours. 

When the tumours were analysed, the researchers found that the virus had reached the target cancer cells. Looking at the tumour samples as well as mouse and cell models of the disease, they also found evidence that infection with the virus switched on the immune system. 

Dr Adel Samson, co-lead author from the University of Leeds, said this is the first time that a treatment virus has been shown to pass through the blood-brain barrier. It acts as a protective layer that keeps potentially dangerous substances out of the brain, but can also stop drugs and other treatments from reaching the brain.

The virus was injected into the patients’ bloodstream, rather than directly into the tumour. So if it is found to be a successful treatment it could be easy to give to patients.

Dr Colin Watts, a brain tumour expert at Cancer Research UK, said the study represents an exciting first step along the journey towards clinical use. 

“They have proven that the virus penetrates the tumour and does what it is supposed to do - wake up the immune system to see the cancer,” he said. “Now clinical trials are seeing if that wake-up call is sufficient to kill the cancer cells and help to improve survival of patients with brain tumours.”

In the second study, researchers from the Ottawa Hospital and the University of Ottawa, Canada, used a similar approach in mice with an aggressive form of breast cancer, injecting a different cancer-targeting virus directly into tumours.

While the virus successfully infected the tumour cells in the mice and killed some, this didn’t have a large effect on tumour growth or how long the mice lived.

But mice treated with the virus had fewer instances of the breast cancer spreading than mice that weren’t infected. 

Melcher said the important study shows that anti-cancer ‘oncolytic’ viruses can boost the immune system to attack tumours. 

The researchers found that genes involved linked to how to immune system is activated were switched on in virus-infected tumours compared to tumours that weren’t treated. 

Treatment with the virus, surgery and immunotherapy drugs that release the immune system’s brakes cured 60-90% of the mice, depending on the type of breast cancer. This was compared to no cures in mice treatment with just the immunotherapy and 20-30% with the virus by itself.

"Our immune system is constantly trying to recognise and kill cancer cells, but the cancer cells are always trying to hide from it," explained Professor John Bell, the study’s senior author. 

"When you infect a cancer cell with a virus, it raises a big red flag, which helps the immune system recognise and attack the cancer. But in some kinds of cancer this still isn't enough. We found that when you add a checkpoint inhibitor after the virus, this releases all the alarms and the immune system sends in the full army against the cancer."

Dr Marie-Claude Bourgeois-Daigneault, lead author of the study, said she believes that the same mechanisms are at work in human cancers, but further research is needed to test this kind of treatment in people.

References

Samson, A. et al. (2018) Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade. Sci Trans Med.

Bourgeois-Daigneault, M. et al. (2018) Neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer to immune checkpoint therapy. Sci Trans Med