Seeing past cancer’s invisibility cloak

In the build up to this year’s Stand Up To Cancer, we’re running a series of posts that focus on the science that is happening around the country thanks to your generous donations and amazing fundraising. The fourth post in our series focuses on immunotherapy.

Immunotherapy drugs, which harness the power of the body’s immune system, are showing great promise as treatments for several types of cancer.

And much of this promise has come from drugs that reveal cancer cells to our immune cells, allowing them to attack what they previously couldn’t see.

But while some patients respond really well to these treatments, they don’t work for everyone. And for those patients that do respond, these drugs can have nasty side effects.

Thanks to funding from Stand Up To Cancer, cancer researchers Professor Chris Rudd and Dr Alison Taylor, are developing new experimental drugs that stop cancer cells being masters of disguise. Leading the research at the University of Leeds, Taylor is being mentored by Rudd from Canada, who originally headed the project.

Masters of disguise

Our immune system is an immensely powerful defence against viruses and bacteria, and even cancer cells.

But cancer cells can be crafty. They use certain molecules as a ‘cloak’ to disguise themselves from immune cells, tricking them into thinking they are normal cells, and not a threat.

Rudd and Taylor’s teams are trying to find ways to help immune cells see past this ‘invisibility cloak’, and spot the cancers cells hiding underneath.

Uncloaking cancer cells

One of the molecules that make up the cancer’s ‘cloak’ is called PD-L1, which sticks to a protein called PD-1 on immune cells. Treatments have already been developed that stop PD-1 from sticking to the PD-L1 ‘cloak’, so the immune cells are no longer fooled by the cancer’s disguise.

The effect was much bigger than anything we had seen before

– Professor Chris Rudd

The duo has been using an experimental drug to block a molecule that helps make PD-1, called glycogen synthase kinase 3, or GSK3.

Blocking GSK3 stops PD-1 being made, says Rudd, and helps kick immune cells into action.

“In mice, we found the immune cells became much more active when we blocked GSK3. The effect was much bigger than anything we had seen before so we were really excited!”

Now they have a drug that successfully stops PD-1 being made in mice, the next challenge is to see if the same occurs in people.

Effective alone, or better together?

The journey to get drugs from the lab bench to the clinic takes time. While giving this drug to mice hasn’t caused any side effects yet, the next step is to make sure it’s safe for cancer patients.

So far, things are looking promising for the team.

“It almost seems too good to be true,” explains Rudd. “Our work is raising our hopes that blocking GSK3 using this drug might be possible without causing a lot of complications and side effects, such as inflammation and autoimmune disorders.“

There may be issues of drug resistance though. “Everyone is different, so a drug is not going to work for everyone,” explains Taylor. “Resistance is an issue with every drug so you have to manipulate treatment, or change a treatment plan a little bit each time. A new GSK3 inhibitor drug would give us more options for patients.”

And Taylor believes that their drugs could also work in combination with other immunotherapies.

“If this drug works in people, doctors could, in theory, either give the GSK3 inhibitor drug alone or in combination with other checkpoint inhibitor drugs like anti-PD-1s, or anti-CTLA4s.

“In our research, we want to know if these therapies act best by themselves, or if they work better together.”

Stand Up To Cancer’s vital role

“Stand Up To Cancer has been really vital for us,” says Rudd. “The work we’ve done wouldn’t have been possible without their funding. By giving us this money, they have put their trust in us and have enabled us to get our exciting work off the ground.

“We’re extremely grateful to them for helping us apply our research to cancer, and we hope it helps patients in the future.”

Taylor agrees: “Stand Up To Cancer’s funding has created a lot of opportunities to take our science further, and to bring scientists together.

“This is incredibly important – it’s how the research moves forward and keeps going.”

Keeping this research going could reveal how to remove the cloak from cancer cells.

And, ultimately, expose these masters of disguise for what they really are. Once and for all.

Catherine