Cellular Highways unveils Highway1 cell sorting prototype

"Upwards of one billion cells need to be processed for cell therapy for one patient, separating a specific cell type with high purity, so it’s a big challenge and there’s no current equipment to sort them.”

Samson Rogers, co-founder and CEO of Cellular Highways, is talking about his company’s new cell sorting capabilities. While the technology isn’t there just yet, the methodology is established.

“The incumbent cell sorting technology, commonly known by the acronym FACS – fluorescence activated cell sorting – has been around since the 1970s but is too slow, difficult to operate, and produces contamination which is a safety risk for both patients and technical staff,” says Samson. “In a typical process, around 20 such instruments would be required to process one patient’s cells in a reasonable amount of time, so it’s generally regarded as unfeasible to use this technology for cell therapy.

“However, such is the importance of cell sorting in cell therapy production that some of the well-funded companies are setting up huge and expensive facilities to use them anyway.”

Cellular Highways was incorporated in April, but the story starts in 2016 when Samson was at TTP on Melbourn Science Park. He’d been with TTP from 2008 to 2012, then left “because I wanted to experience something different; I was away for three years, and after an MBA and two start-ups, was attracted back to TTP by the new generation of TTP management who wanted to do new enterprises and spin-outs, including Matthew Carr and Sam Hyde”. Today, Matthew is head of life sciences and chair of Cellular Highways, and Dr Hyde is TTP’s managing director.

“Early in 2016 we decided to do cell sorting,” Samson says. “We didn’t have any technology in that space but were interested in cell therapy. Cellular immunotherapies were developing fast and we saw a need for a tool to sort and purify cell populations that involved autologous cell technology, which means cells taken from a patient’s blood, grown to a large batch and injected back into the patient to target cancer.”

The cells need to be sorted at scale, with high-quality, consistent, results.

“It’s hard to do – indeed out of all equipment challenges to process the cells, sorting is the hardest bit.”

By 2017 progress was good.

“Cellular Highways was incubated in the life science department at TTP,” says Samson. “TTP was putting in resources to build the technology. Having decided to go for a cell sorter for cell therapy, by 2017 we had an excellent team, including physicists Robyn Pritchard and Alex Zhukov, and had invented a device that really worked. By 2018 it was still a demonstrator but the core device looked quite mature. In 2019 the decision was taken to lead its commercialisation and spin out of TTP.”

Cellular Highways started life with the biotech equivalent of a silver spoon in its mouth: a new microfluidic cell sorting product using VACS – vortex actuated cell sorting – alongside an established investor. Called Highway 1, the first prototype will be unveiled later this month at CYTO, the 34th Congress of the International Society for Advancement of Cytometry, in Vancouver. TTP, who have already invested £2million in the concept, recently invested a further £1.7million to get the bench-top cell sorting instrument up and running. Cellular Highways is so new it is still based at TTP’s premises on Melbourn Science Park, although a new site elsewhere on the park is on the cards.

“The Cellular Highways route has been part of the discussion from the start,” says Samson. “This sort of development requires a lot of investment – like anything in biotech – and it’s great that TTP can do this at an early stage. There’s been continuous investment while incubating at TTP and now the funds that are available will be used to develop the team, the materials, expenses – especially micro-fabrication, internal and external suppliers, because this is about developing hardware from scratch. Nothing goes smoothly, it’s one step forwards and two steps back every day!”

The next few weeks after the Vancouver unveiling of the prototype will be huge.

“After that, we’ll be getting feedback, finding out how the user interacts with it, which is hard to guess... in the next three to six months we’re getting ready for beta testing with cell therapy partners and others. This is very important as the research community may only be a few thousand people but they’re doing things that are going to be huge.

“To identify circulating tumour cells from a liquid biopsy – we’re going after that too,” adds Samson. It has always been a challenge to diagnose cancer in its early stages, especially without the risks of invasive surgery.

“The dream is to diagnose cancer from the blood, and the big challenge is to find elusive cells in the blood that shouldn’t be there – circulating tumour cells, which might be present in tiny numbers; ten cells out of a billion, say. If these can be separated, then they can be characterised in the lab to diagnose if they are indeed part of a spreading cancer.”

Once you’ve got this data at your disposal there’s lots more you can do with it – such as gene editing.

“There’s a trend in drug discovery,” explains Samson, “to applying gene editing across the genome, so that means a pool of cells where every single gene has been knocked out... to cover the whole genome typically needs a pool of thousands of millions of cells.

“The way of linking a candidate drug molecule to the function of individual genes is to have a big pool of cells, with cells in that pool where every gene has been knocked out by gene editing – a genome-wide CRISPR knock-out pool. You have to have a process to pick out these cells – the ones demonstrating some phenotypic change, so you can analyse their genome. There’s no current way of sorting that many cells.”

After Highway 1 comes Highway 16, which is capable of having “a billion cells analysed in an hour... between 10 and 20 times faster than competing techniques”.

Making a “sterile cell sorter for the laboratory means, potentially, tens of thousands of labs”. The potential for cell therapy alone could mean enabling more sophisticated therapies, where a patient’s white blood cells are reprogrammed in new ways, with the reprogrammed cells reintroduced back to the patient.

Beyond T cell therapy are therapies based on other kinds of cells including regulatory T cells, natural killer, and progenitor cells – which are all in reach, perhaps within five years. As well as creating new therapies, the arrival of this new cell sorting technology will also look to make existing therapies faster, more effective and more affordable.

Better cell sorting available in every lab is an admirable goal. The pace might mean that it’s not out there for two years, and it’s not yet clear whether the new biotechnology will be offered as part of an all-round service or as a single-item sale, but these are details. Details which, of course, we will be reporting on every step of the way.