How has the cell therapy landscape evolved in the past ten years, particularly in regard to the utilization of iPSCs?
That's a great question, and it's been great to see the field evolve in the last ten years. If I think back to 2012, there were a few cell therapies that involved iPSCs in the field of regenerative medicine. They mostly focused on diseases such as macular degeneration because the eye is an immune-privileged organ, making it easier to develop therapeutics. Today, if you carry out a search, there are over 100 iPSC-based clinical trials. About a fifth of these are using iPSCs as therapeutics and they are now covering a much larger variety of diseases - anything from hematological to cardiac to neurological and many others.
What has been even more exciting is that since 2020, with the rise of autologous cell therapies, we have seen iPSCs starting to play a role in immune cell therapies as well. A small number of developers are now supporting iPSC-based immune therapies in clinical trials. We hope that the next step in the iPSC field will see more autologous therapies being replaced or supplemented with allogeneic iPSC-based cell therapies.
What are today’s greatest challenges in iPSC-based allogeneic cell therapy development?
There are a few details that require our attention. One reason to be concerned with safety is the karyotype stability of iPSC-based products. Many of the processes that the cells go through, for example, reprogramming, genome editing and subsequent differentiation can impact their stability. However, this can easily be addressed through rigorous genotypic screening, both for the master cell banks of iPSCs and the final products.
A second challenge that is important to address is histocompatibility. It’s important to ensure that after transplantation, the host will not reject the cells but also that the transplanted cells will not attack the healthy cells of the patient. Therefore, introducing HLA modifications helps to address this issue and provide safe and efficacious allogeneic cell therapies.
What strategies and capabilities seem best primed to increase reproducibility and scalability, and reduce costs in iPSC manufacturing?
There are a lot of strategies I could mention here. In terms of reproducibility, it's important to understand the process from the beginning and to define what parameters you will be monitoring and define what the product will be. This is called defining the quality target product profile, which needs to be done very early on. Once you understand what you want to achieve, what becomes important for reproducibility is to have very rigorous in-process monitoring. Identify parameters that can influence the outcome of the process and ensure that these remain within the accepted criteria during product production and manufacturing.
In terms of scalability, I know that this may sound counterintuitive, but it is important to firstly identify a small-scale system in which you can optimize the process. Manufacturing at scale is very costly and it doesn't allow for multiple round of optimization to be carried out. However, if a small-scale system is identified then you can easily vary and investigate the different media, cytokines, matrices, and physical parameters that can impact and improve the process. Then, as a second step, you can use smart tools such as artificial intelligence and mathematical modeling to help translate these small-scale systems into large-scale systems.
And of course, to reduce costs, a lot comes down to the reagents. It's important for developers such as Cellistic to continue monitoring and testing cheaper alternatives to some of the key reagents that are adding to the cost. Another way to reduce costs is to reduce the length of the manufacturing process. These are factors that we currently focus on during our product and platform development work.
How is Cellistic positioned to satisfy the unmet needs and challenges of the industry?
Cellistic is an experienced partner that has built a team able to expedite product development processes and catch some common pitfalls that people might encounter if they're new to the iPSC-based manufacturing process. We have built our team of experts with a deep understanding of immuno-oncology and iPSC biology but also of quality, regulatory, manufacturing and scale-up requirements. We strive to understand and standardize our processes to be in a good position within the industry and to provide successful allogeneic cell therapy manufacturing for our clients.
What is one recent piece of iPSC news/research that has stood out to you and why?
Considering the fundamental goal of what we do is to serve patients, as they are the ultimate beneficiaries of what we work on day-to-day, I would have to choose some of the recent iPSC-based clinical trials. We are eagerly awaiting results from several clinical trials, for example, those from Fate Therapeutics (CA, USA). They have several candidates in trials for multiple myeloma, acute myelogenous leukemia, chronic lymphocytic leukemia and B-cell lymphoma. It's really exciting to see these products moving into the clinic, and we're looking forward to seeing the outcomes of these trials.
How do you envision iPSCs changing the future of cell therapy development?
That's a great question. Currently, autologous cell therapies are utilized to treat patients that have perhaps exhausted all other therapeutic options, and can cost up to a million dollars per patient. Therefore, these are not widely available or affordable to many patients.
We envision iPSCs changing the future of cell therapy by enabling large-scale manufacture of off-the-shelf therapies, which will greatly decrease the cost per patient. As well as this, it will make therapies more accessible and patients won't have to exhaust all other therapeutic options before receiving cell therapy. We envision that this can potentially be a first-line treatment, and this will ultimately benefit the health of these critically ill patients.
Editor’s Note: This interview previously appeared on www.regmednet.com.