Epigenetic cancer tests for both ends of the leash.

Cancer diagnostics is advancing rapidly for both man and dog thanks to nucleosomes research

By Jacqui Thornton, health journalist

The treatment of cancer has improved exponentially in the last two decades, with targeted therapy, personalised medicine and robotic surgery. Diagnostics for cancer could be seen as the poor cousin to therapeutics, less well funded, and not as visible.

But advances in the understanding of epigenetics and nucleosomes – basic units of DNA within cells - has led to an exciting new platform with multiple applications to diagnose cancer, test for remission and monitor drug efficacy.

VolitionRx was established 12 years ago to capitalise on this science. The co-founding scientists were two chemists Jake Micallef, with a background in developing blood tests for the UK NHS and the World Health Organization, and Mark Eccleston, now Chief Technology Officer, who had met working at the same pharmaceutical company.

Alongside Australian entrepreneur Cameron Reynolds, CEO, their aim was to transform cancer diagnostics from expensive, invasive and often unpleasant procedures to something as fast and accessible as cholesterol or pregnancy testing.

The company went from having a single two-meter lab bench at the University of Namur in Belgium for R&D to a purpose-built 20,000 square feet lab in Crealys Science Park, in Gembloux and an Innovation Lab in California in addition to further offices in London, Singapore and Texas.

By 2018 they had 40 employees, yet despite significant progress in nucleosomes research and their Nucleosomics platform, which they trademarked, they were still at an early stage of assay development for the range of human cancers they were working on - colorectal, lung, pancreatic and prostate.

It was a meeting between Heather Wilson-Robles, a veterinary medical oncologist and at the time Associate Professor at Texas A&M University, and Jason Terrell MD, Volition’s Chief Medical Officer, in 2018 that turbo-charged the research – and created a whole other side to the business in diagnosing cancer in canines.

And because research on diagnostics for dogs can be done in a quicker time frame due to swifter processes and speed of disease progression, remission and recurrence, the veterinary results were able to inform the work in humans.

At the heart of the company is Nucleosome Quantification (Nu.Q®) technology measuring the structure that contains epigenetic modifications. This is the core technology, the platform that runs across all their efforts.

Whereas traditional genetic tests look at specific pieces of DNA in cells, the Volition platform searches for epigenetically modified nucleosomes in the blood, shed by cancer.

During cell death, fragments of the chromosome are released into the blood as nucleosomes. Certain diseases, such as cancer and inflammation, can lead to increased concentrations of circulating nucleosomes in the blood in the form of cell free DNA.

Terry Kelly, Chief Innovation Officer, says that as well as detecting the presence of cancer cells, these nucleosome tests might be able to detect recurrence earlier, spot treatment-resistant mutations and whether a cancer patient is no longer responding to a treatment.

Up until the meeting in Texas, the team had only been looking at developing diagnostics for humans, although they had done some work with horse and dog samples.

But as human and mammal nucleosomes are almost identical the Volition team thought there could be some synergy and saw a collaboration with Texas A&M as an opportunity to expand the utility of Nu.Q®.

Heather Wilson-Robles already had a special interest in translational medicine – studying how research in animals could be translated into humans. But she had never heard about nucleosomes – and was intrigued.

Her research over 15 years has focused on improving canine models of paediatric and adult cancers and translating these findings to the mutual benefit of both species. Her basic research focuses on the identification and targeting of the tumour initiating cells in osteosarcoma, melanoma and mammary/breast cancers in both canines and humans.

Heather began her own research using Volition’s Nucleosomics platform, with a proof-of-concept study using samples of healthy and diseased dogs from a biobank, followed by pre-analytical work.

In 2019 a Memorandum of Understanding was signed between Volition and Texas A&M and later that year Volition Veterinary Diagnostics Development, an animal health subsidiary to its human life sciences division, was formed, with the University owning 12.5%. The following year Heather was appointed CMO, and research continued, published in peer-reviewed journal PLOS One.

In December 2020, the first product, the Nu.Q® Vet Cancer Screening Test was launched – described as a ‘stand out moment’ and a milestone in their 10-year history by Cameron.

While the veterinary work seemed super-fast, it benefitted significantly from the 10 years of work Volition had done understanding the biology of circulating nucleosomes and building the platform. In a positive exchange, the work in dogs gave Volition more understanding and insight into the human research – and set them on the track of using nucleosomics to diagnose non-Hodgkin’s lymphoma.

And they were right to do so – they got the best single assay results they had ever had in blood cancer for humans. Both ends of the leash – dog and human – were winning.

Jake Micallef, Chief Scientific Officer, explains that chromosomes and nucleosomes have the same structure across species. “A nucleosome in a dog, or a cat or a horse or even yeast is pretty much the same. So, our test works in all kinds of species and certainly in all mammalian species. We've tried half a dozen. The principles are the same and what's been really helpful I think is that there has been synergy both ways.”

He said part of the reason the technology took off in dogs was the understanding that the diseases most amenable to our approach - blood cancers - are very common diseases in dogs. “Heather has been able to do a lot of studies in dogs very quickly, that we wouldn't be able to do as fast in people because processes are slower.”

Terry agrees. “The disease course within a dog, at least with cancer is so much quicker. They can get cancer, go into remission and come out of remission in a year. Trying to do those types of studies in humans is much more difficult.”

Since launch, the vet side advanced rapidly, with papers published in 2021 which found that the Nu.Q® Vet Cancer Screening Test detected 82% and 77% of canine hemangiosarcoma and canine lymphoma cases respectively with specificity of 97% - these alone represent almost one third of all canine cancers.

The company is now looking at tests for other species, such as cats and is in the exploratory phase for horses. While there are other liquid biopsy tests like this for animals on the market, Volition says their advantage is simplicity, lower cost and faster results.

They are also studying the possibility of tests to analyse if dogs are coming out of remission from cancer – an early warning system.

In humans, the research is now coming on apace too, despite the COVID-19 pandemic causing challenges.

The company is currently conducting large human trials focused on colorectal and lung cancer and is also conducting a small proof of concept monitoring study in diffuse large B cell lymphoma (DLBCL), a subtype of non-Hodgkin’s lymphoma.

The tests will not definitively prove someone has cancer, but they are a very good indication that someone does not have cancer.

Heather, who retains her Professorship position at Texas A&M, says what has impressed her about the Volition ethos is their commitment to both humans and animals, and their obvious love of science.

She says: “Most of the human companies I work with in a collaborative way want to use the dog to help get their product approved, and then they have no interest in helping the dog after that, with a few exceptions.

“Volition haven't just used the dog to promote their human work, they’ve invested in it equally. They also see the value in investing on both sides of the market. And I think probably that’s because a lot of the people in the company have big hearts and they have dogs, and they just love the area.

“It's exceptionally rare to have a company where you've got people like Terry, Jake, and I talking on a regular basis just about science. I have never ever had that anywhere else.”

-ends-

Find out more...

About Jacqui Thornton

About epigenetics and Volition's Nucleosomics™ technology

About Nu.Q® Vet Cancer Screening test