By Kathryn Golden, SVP Technical Operations & Cell Manufacturing bit.bio
The Power of a Cell
The revolutionary impact of human cells as therapies has already become apparent. So called CAR-T-cell therapies—when T cells are engineered to become CAR-T-cells, by adding a specialised receptor able to detect and attack certain cancer cells specifically —are able to cure blood cancers that used to be untreatable. The engineering of this single cell type has sparked the first wave of cell therapy companies. This is the beginning of a new industry that will harness the regenerative power of many more cells in the human body. Every single cell type has the potential – just like the T cell has with CAR-T – to give rise to multiple next generation therapies, and possibly entire industries.
There are a vast number of different cell types and each has a unique role. Neurons transmit nerve signals from one place to another, whereas muscle cells form the fibres that enable movement. However, despite their differences, all the cells in the body contain the same DNA.
The idea of cell therapy is a new way to approach human health and usher in a new generation of treatments for diseases that have proved too complex for more established types of therapies – such as small molecules that normally come in the form of a pill. A cell therapy uses human cells as the treatment. It’s a way to leverage the human body’s natural and effective disease-fighting system – for example, when exposed to an immune response trigger, our bodies are prepared with a complex and effective plan of action involving cells with various roles to effectively treat the issue.
The Need for Low-Cost Treatments
All of the current cell therapies that are on the market are CAR-T therapies. These therapies use cells taken from the patient, which are modified, and reintroduced into their bodies. A single course of one of these treatments has been recorded to cost up to $475,000. This high price tag is due to the bespoke and personalised nature of the therapy. Once the cells are retrieved from the body, the process of modifying them can take up to 3 weeks of complicated laboratory work before treatment can even begin, which contributes to the high final cost. This is an autologous approach. The alternative is an allogeneic approach, where the T cells come from a source other than the patient being treated.
For the true benefits of cell therapies to become commonplace and affordable we must pursue the development of “off-the-shelf” allogeneic approaches. This kind of treatment would be cheaper and more readily available for most patients, but widescale rollout is prevented by cell manufacturing bottlenecks; it requires that a huge number of cells are manufactured, and that every cell has the same characteristics – or to put it another way, the cells must be of a quality that is suitable for a medicine. This is a huge challenge and we need huge volumes – trillions of cells if we want to treat millions of patients at an accessible cost.
To unlock this type of treatment, a new approach for how we manufacture human cells for therapy is needed. At bit.bio, the solution we are working on is a synthetic biology approach – precision reprogramming human cells or coding human cells.
Human induced pluripotent stem cells, or iPSCs, are the starting point for this approach – these cells are the starting point for every cell in the developed human body. They are like a blank slate when it comes to their identity – they have limitless possibilities for what they can turn into. Our opti-ox technology allows us to ‘code’ or reprogram these cells at the DNA level, driving them into a new identity of our choosing, depending on the code we insert into the DNA. And opti-ox has unique properties that allow us to do this consistently, overcoming a problem called gene silencing – where the stem cells can switch off the reprogramming and not convert. Consequently, for the first time, it is possible to see how we can manufacture highly consistent batches of human cells at scale with precisely defined functionality and unprecedented quality. It’s this technology that makes me excited to work at bit.bio – as I believe with this approach, the bottleneck of access to a reliable, scalable supply of human cells for therapies is removed. Like most scientific endeavours, it’s not as simple as it sounds and we have many hurdles to overcome. But I think with a programming approach, accessible cell therapies for millions of patients will become a reality.
Kathryn Golden is an accomplished CMC executive with a track record of shepherding complex drug candidates from discovery stage to pivotal trials. Her expertise includes integrated process development, phase-appropriate quality and regulatory coordination, and management of contract manufacturing organisations. She has been an early employee at six biotechnology start-ups, including Q32 Bio and Codiak BioSciences. Kathryn is particularly passionate about increasing access to transformative therapies and is a co-founder of Sunflower Therapeutics, a start-up utilising yeast manufacturing technologies to provide biologics at point of care to underserved populations. Kathryn received her S.B. in Chemical Engineering and M. Eng. in Bioengineering from the Massachusetts Institute of Technology and holds an M.B.A. from the Sloan School of Management at MIT.