Spin-out Cellular Highways looks to next-generation cell-sorting

There is no cell purification technology that allows the selection of cells based on several molecular markers at the same time while processing large batches of cells. That is until the VACS platform, new entity Cellular Highways claims.

Tech firm TTP has invested £1.7 million ($2.2 million) in its spin-out firm Cellular Highway in efforts to commercialize the Vortex-Actuated Cell Sorting (VACS) platform.

Bioprocess Insider (BI) spoke to Salman Samson Rogers (SSR), CEO of the new entity to find out more about Cellular Highways and its VACS technology.

BI: What are the issues in the biopharma industry Cellular Highways is looking to tackle?

SSR: For any new therapy, it is a huge challenge to translate basic biology into clinical trials, and eventually roll the therapy out into mainstream medicine. Even more so for cell therapies: the autologous CD19-CAR T-cell therapies Kymriah and Yescarta have shown the tremendous power of cellular immunotherapies against cancer, yet they remain – in cell therapy terms – very crude examples of what might yet be possible. These approved therapies target an entire type of white blood cell: the B-cells. This is ok for cancerous B-cells, because although obliterating the B-cells does indeed have health impacts, one can live without B-cells in the long term. But for many other types of cancer, the targeting of the right cells is a much greater problem.

To do this, scientists are exploring much more sophisticated ways of using the patient’s own T-cells – including subtypes of T-cells – and genetically programming them in much more sophisticated ways. A key tool that scientists doing this require is a cell purification technology that allows them to select cells based on several molecular markers at the same time, while processing large batches of cells – upwards of a billion cells – in fully sterile conditions. To date, there is no current good way of doing this, and it is a challenge right through cell therapy: from the early stage development, through clinical trials, all the way to eventual large-scale manufacturing.

BI: So how will your VACS platform help overcome this?

SSR: With the VACS technology, Cellular Highways intends to provide this tool, to enable purification of large batches of cells according to multiple molecular markers, in fully sterile conditions suitable for Good Manufacturing Practice (GMP) therapy production.

The issue that VACS resolves is scalable sorting of cells based on multiple molecular markers, i.e. larger batches of cells in a practical amount of time, in conditions that are suitable for cell therapy manufacturing, i.e. free of contamination, cross-contamination and biohazardous aerosols. This enables new cell therapies that might not otherwise be possible. In technical terms, the main innovation of VACS is to make faster cell sorting possible in an enclosed microfluidic device. The big challenge in making cell sorting faster, is actually to make a cell sorter smaller, so that many such sorters can be laid out in parallel on one microfluidic chip for real time optical interrogation. This is because the limit of cell sorting speed is caused, not by any limitations on the device hardware, but by stress on a cell forced through a narrow channel or orifice.

BI: So how does VACS work?

SSR: The core device of VACS is the smallest high-speed cell sorter in the world, with an ‘sort envelope’ speed of 43 kHz which compares well to FACS, the incumbent cell sorting technology that is widespread in biological research but unsuitable for the clinic. The difference is that VACS has a footprint on chip of 1 x 0.25 mm, including its actuator and plumbing. This makes parallel sorting much more practical than any previous technology – we have just got our first results on a 16-plex parallel sorting chip, i.e. using the same core device. This is a major technical feat that we are very proud of.

BI: Is there any similar technology available to the industry? If so, how does this differ?

SSR: This need has been around in the biotech industry for a long time for a long time – to sort a couple of billion cells within a few hours, based on multiple molecular markers, at high purity and high yield, in GMP conditions. The incumbent technology in cell sorting, commonly called FACS, is about fifty years old, and has reached its natural limits in terms of cell processing speed. The complexity of the technology means that it is very hard to scale by parallelization, and because of the high voltages and droplets flying through the air, it is very hard to enclose in a single-use sterile consumable. Despite this, the desperation of some cell therapy companies is such that they have set up cleanrooms with tens of FACS instruments, all processing aliquots of one patient’s cells, in parallel at the same time. This is a processing nightmare, and not likely to get them far.

Others have responded to the need in various ways. Other candidate microfluidic sorter technologies have emerged in the last decade, including two main commercial efforts. But both have severe limitations because of the physics of the basic technology, especially when it comes to scaling. Then there are bulk cell separation technologies, using matrix adhesion or magnetic particles to enrich cells, i.e. not sorting based on flow cytometry. These technologies are typically good for separating based on a single molecular marker, but rapidly get complicated when sorting based on more than one marker is required. There are also cell therapies which use cytokines and other elements of selective culture to grow the right cells – but these biological routes are far from trivial too.

In Cellular Highways, we have already overcome the main hurdle to scaling cell sorting. While we are still developing our products, the technology now has a clear route to fulfilling this need in cell therapy.

BI: Finally, can you talk us through your business model?

SSR: The first stage of Cellular Highways’s business strategy is to launch a VACS benchtop cell sorter instrument for research use, which we have named “Highway 1”, and are planning to unveil it at CYTO 2019 in Vancouver, this June. The reason why it is important to first launch a research instrument is that the most important biotech applications, cellular therapies and liquid biopsy diagnostics, are largely still at the research stage, and it is important to give scientists the tool that they need as they investigate translating their discoveries to the clinic. Beyond that, we have had our first successful feasibility results on the parallel scale-up version, which we call “Highway 16”, which we also plan to commercialize as a research instrument within 2-3 years. For research use, Highway 1 and Highway 16 will be based on a simple business model: instrument and consumable sales. The consumables are the single-use sterile sort cartridges, which we intend to price attractively, so that it is widely adopted by scientists.

Beyond this, for clinical use, the business model is hard to predict, because the business models of the cell therapy companies themselves are rapidly evolving, and the healthcare industry is only now working out the logistics and charging models to distribute them. Moreover, unlike bone marrow therapies back in the 90s, which were regulated as medical devices for autologous cell enrichment procedures, the present generation of cell therapies are regulated as a drug. This means that each cell therapy company must take responsibility for all equipment used in its manufacturing process, and therefore has particular requirements for equipment, including security of supply. Most likely, this means will enter into a supply partnership with each cell therapy company that wishes to use our products in manufacturing, and customize our products for their use.