By Mary Ann Labant
The production of living cells as a therapeutic product is a complex process. To date, autologous cells constitute the majority of clinically evaluated CAR-T cell products. Although autologous therapies can indeed be effective and life-changing for patients, this approach poses time and logistical constraints. Allogeneic cellular productsgenerated from cells from healthy donors, can potentially overcome these limitations and enable the generation of “off-the-shelf” products.
But the technologies, solutions and equipment needed to bring allogeneic cell therapies to large-scale clinical trials and global commercialization are not yet commercially available and that is, in addition to the biological challenge of ensuring immune evasion of these cells, one of the main bottlenecks facing researchers. Industry.
“Allogeneic stem cell therapy is exciting because a stem cell has the potential to differentiate into almost any type of tissue cell and therefore can attack the root cause of a wide variety of diseases,” said Thomas Bieringer, PhD, technical manager at Bayer.
To realize the potential of using healthy donor stem cells as a basis for cellular therapies, the cells must be programmed to avoid attack by the recipient’s immune system. Recent developments in gene editing technologies support strategies to engineer immune evasion.
“So now we have the foundation to move from single-patient autologous therapy to one-to-many allogeneic therapy. However, we need the technologies, solutions and equipment to make this possible,” emphasized Aaron Dulgar-Tulloch, PhD, Chief Technology Officer at Cytiva. Cytiva and Bayer share a common vision and understanding of the challenges that limit the progress of allogeneic cell therapy and believe that together they can overcome these challenges.
THE companies collaborate to build a fully automated modular platform that can be used for scale-up and manufacturing of multiple cell therapy products. The concept will use fully characterized individual equipment modules that can be incorporated into a plug-and-play scenario. Dulgar-Tulloch and Bieringer believe this will speed up the learning curve.
Human cells are fragile
Treating living cells as a therapeutic product makes the processes more complex than traditional biotherapeutics. Depending on the therapeutic application, different cell types must be treated. These cells, which may need to be cultured as aggregates, cell suspensions or single cells, exhibit higher sensitivity to nutrients and wastes compared to conventional bioproduction cell lines.
Essentially, cells want to “feel good” in the corresponding reactors, which means they need the right composition of media. Additionally, oxygen transfer and metabolic stress must be precisely controlled. To provide cells with an optimal environment, the underlying biological process and equipment performance must be optimized.
The development of this user-centered manufacturing platform aims to meet the sensitivity and requirements of different cellular systems, work with a variety of model systems including different cell types, and use a wide range of tools modeling and laboratory experimentation.
Enabling genomic medicines
The collaboration focuses on what the companies envision the entire field of genomic medicine needs to bring cellular therapies to patients more quickly. “If we are successful, we believe that the entire community of therapy developers, technology providers and, most importantly, patients, will benefit from accelerated, cost-effective and globally available allogeneic cell therapies,” he said. declared Dulgar-Tulloch.
The process started by aligning with the platform boundary conditions, i.e. how to define modularity (plug-and-play hardware and software), automation and the concept of process control . The initial focus is on two components that are currently in immense need: a 3D expansion system for large-scale production and a robust harvesting solution. As additional needs are identified, other devices may follow.
The ultimate goal is to gather insights and provide solutions to a broad range of users, leading to the creation of a consensus allogeneic cell therapy platform. Bieringer emphasized that this will generate economies of scale and simplify global manufacturing, thereby reducing costs to make allogeneic cell therapies more accessible.