The emergence of cell-based therapeutics is one of the most important human stories of our time. Rapidly advancing technologies and techniques are continuing to transform medicine across a wide range of disease areas. But as with all opportunities, cell therapies come with great challenges, not least the extremely high cost of manufacture. For us, the drive to democratise the new therapies – to make them affordable and accessible to as many people as possible – has begun.

We must stress that it’s very early days, but the bioengineering team here at CC is committed to a path of discovery that is focused on the possibilities of using synthetic versions of human cells. It forms part of our wider vision for highly-scalable, high-throughput, cost-effective cell therapy manufacture. Synthetic cell research of this kind is currently mostly restricted to academia, but we are exploring it as a viable and attainable next step on the journey from autologous to allogeneic cell therapy.

Before we dive into the detail of that, let’s set the scene with a bit of background and perspective. Scientific and technological advances such as gene editing, automation and iPSCs (stem cells extracted from adults instead of embryos) have already revolutionised modern therapies and personalised medicines. Autologous immunotherapy, whereby a patient’s own cells are re-engineered for therapeutic purposes, was – and still is – ground-breaking. A patient’s immune system is leveraged to heal itself from the inside out, avoiding the chokepoint of immune rejection typically seen in other cell-based therapies.

The resulting therapies offer a highly specific, minimally invasive and very effective means of treatment – for example, in eliminating all cancerous cells from a patient without radiation or chemotherapy. Plenty of limiting factors remain in areas like process control, throughput and batch release criteria, but the overriding problem is the vast price tag associated with their manufacture.

The complexity of using living cells

Complicating matters further is the sheer complexity involved in use of living cells. The extraction to infusion pipeline is peppered with pitfalls that can lead to loss of cell product. This situation is often compounded by a limited supply of cells from patients in later stages of severe diseases. They can be unable to readily donate large volumes of blood, in addition to being subject to time-sensitive cycles of immunosuppressants.

To date, CC’s pioneering work has been mainly concerned with developing the specialised equipment that companies need to produce their therapies. Because of the unique nature of each application, the resulting bespoke equipment tends to be expensive, limited in breadth of application and liable to rigorous protocols for priming, cell modification and cleaning. The cost of developing these to the FDA’s cGMP (Current Good Manufacturing Practice regulations), including the administrative burden and operational facilities, is huge. The upshot of all this is that cell therapy manufacture can take many days – and even months – for a single patient dose.

Eliminating the need to use the patient’s own living cells as a delivery vessel represents a gamechanger for advanced therapies. This brings us to allogeneic cell therapy, where the immune cells utilised are taken from another person’s blood. This is more cost efficient because of the lack of patient specificity required, allowing one cell source to potentially service many different patients. On the downside, both the risk of graft versus host disease (GvHD) and the cost of manufacture remain high. Efforts to overcome these issues have centred on reengineering the human leukocyte antigen (HLA) gene on donor cells to reduce immune responses, as well as the use of donors with rare HLA types (‘universal donors’). Increased automation of the manufacturing process is another hot area of activity.

The challenges that really matter

So far so good then. We’re heading in the right direction – but can we do even better? At CC, we share a vision of a future unconstrained by current thinking. This is more than just a slogan on the boardroom wall, it’s an attitude that propels our collective ambition to overcome the challenges that really matter to people and to business.

Our synthetic cell initiative falls squarely into this category. Could synthetic cells be the next crucial step in the evolution towards affordable, off-the-shelf therapies? Could they allow us to address FDA safety concerns around the oncogenic potential of engineered human cells? And could they mitigate human response issues, reduce manufacturing and therapy-to-vein times and provide a financially viable option that’s open to everyone, including those in the developing world?

The team is actively addressing these questions as we begin to explore the foundations of a high-volume yet inexpensive cell-making process. Early research in our in-house labs is focused on encasing cellular material into a sphere that replicates a living cell. Essentially, we’re applying a bottom-up biology approach to simulate a biomimetic system that works with the body – not against it. This is allowing us to embark on a series of experiments aimed at progressing the manufacturing process in a reliable and high-throughput way. The approach tallies with our vision for an ‘off-the-shelf’ future where cells can be tweaked to treat many conditions in many different people, including rare cancers, autoimmune disease, neurological problems and more.

Progress is steady and initial results are heartening. And there’s no doubt that the notion of synthetic cell therapy is gaining traction across the industry. At our recent virtual visit to SynCell2022, the International Conference on Engineering Synthetic Cells and Organelles, we were struck by an interesting trend. Many academics working in the field are transferring their activities into ambitious start-up companies. The task of scaling-up commercially-viable synthetic cell therapy solutions could be coming around sooner than many anticipate. Watch this space – and do please drop us an email if this is an area of innovation that resonates with you. It’ll be great to continue the conversation.

Co-authored by Ellen Simmons,Senior Biomedical Engineer

Karen Weisinger
Author
Karen Weisinger PhD
Head of cell biology, US; Global Med Tech

Karen has over 15 years of experience in several fields including iPSCs, neurodegenerative disease modelling, cardiac regeneration, and synbio for cancer immunotherapy. She currently leads the Boston based biology effort to support clients with their ambitions in the cell therapy space.