Editor’s Note: In this installment of Expert Opinion, Elena Matsa, PhD, VP of Cell Technology at Cellistic, answers questions about the role of allogeneic treatments in the future of cell therapy
You’ve mentioned before that allogeneic treatments are likely to be critical in the future of successful cell therapies. Why? What are their inherent advantages?
Allogeneic cell therapies have a few clear and important benefits over autologous treatments.
First, developing an autologous therapy is both lengthy and costly. It can take at least six months and cost more than half a million dollars per patient. For a lot of patients, that math doesn’t add up – they simply can’t afford the time or costs involved. When you generate an allogeneic product that is the same for multiple patients, though, the development process is more standardized and predictable, which leads to a higher success rate. And you can greatly reduce costs and can bring therapies to patients in less time.
Second, if your patient is carrying a genetic mutation, the cells that are used for autologous therapy development will carry that same mutation forward, putting the function of the transplanted cells at risk. But allogeneic cell therapies can be sourced from donors with healthy characteristics, resulting in a better therapeutic outcome.
So those are the “pluses.” What are the potential “minuses”? What are some of the obstacles that have to be successfully hurdled?
One big obstacle for allogeneic cell therapy development is histocompatibility.
When using cells derived from donors, you need to make sure that HLA molecules are compatible to avoid your patient’s cells killing the transplanted cells . . . or the other way around. Graft-versus-host disease is a serious risk, so it should be considered from the early stages of your development process. Through genome editing or creating HLA homozygous donor banks, you can ensure that doesn’t happen.
Safety is one of the other main factors for regulatory approval, and karyotype stability is the main safety concern in allogeneic cell therapy. Culturing in an artificial environment, programming and genome engineering can cause cell stress, which can result in the cells gaining karyotype abnormalities. You should minimize this risk through both characterization of your master cell banks and end products, and through genotypic screening.
Inefficient manufacturing can be another obstacle. That’s one we’re working to overcome at Cellistic. We’re leveraging our expertise in iPSCs to pursue the kind of differentiation and scale-up that’s required for successful clinical to commercial allogeneic cell therapies.
Speaking of manufacturing, what should you consider when developing a successful allogeneic cell therapy manufacturing process?
The first step to a successful manufacturing process is to understand the product you want to develop, so you have to begin with your end goal in mind. What’s your target product? What do you want to achieve? That means you should define your quality target product profile (QTPP) very early on.
Then, you should make sure that the manufacturing process you’re building is robust and reproducible. Every batch that you manufacture needs to have the exact same outcome. Small changes in just one of your parameters can affect your end product. You need to understand how these parameters affect your process and how to get and keep them exactly right.
Finally, your process needs to be fully documented and traceable to get through audits and IND filing. The traceability level that is needed for clinical use of your cell therapy can be achieved with digitalization of your processes.Apart from the practical assets of your manufacturing process, you also need a team with not only a deep understanding of immuno-oncology and cell biology expertise, but also of the quality, regulatory, manufacturing and scale-up requirements for successful allogeneic cell therapy manufacturing. This team can be constructed using in-house expertise and/or by collaborating with an experienced partner.