By Mary Ann Labant

Producing living cells as a therapeutic product is a complex process. To date, autologous-based cells comprise 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 logistics constraints. Allogeneic cell products, generated using cells from healthy donors, can potentially overcome these limitations and provide 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, besides the biological challenge to guarantee immune evasion of these cells, one of the key bottlenecks facing the industry.

blood drawn
To capture the potential of using healthy donor stem cells as the basis for cell therapies, cells must be programmed in a way to avoid attack by the recipient’s immune system. [Stefania Pelfini, La Waziya Photography/Getty Images]
“Allogeneic stem cell therapy is exciting because a stem cell has the potential to differentiate into almost any kind of tissue cell and therefore can address the root cause of a huge variety of diseases,” said Thomas Bieringer, PhD, technical leader, Bayer.

To capture the potential of using healthy donor stem cells as the basis for cell therapies, cells must be programmed in a way to avoid attack by the recipient’s immune system. Recent developments in gene editing technologies support strategies to design immune evasion.

“So now, we have the basis for moving from a single-patient autologous therapy to a one-to-many allogeneic therapy. However, we need the technologies, solutions, and equipment to make that possible,” pointed out Aaron Dulgar-Tulloch, PhD, chief technology officer, Cytiva. Cytiva and Bayer share a vision and common view of the challenges limiting the advancement of allogeneic cell therapy and believe that together they can overcome these challenges.

The companies are collaborating to build a fully-automated, modular platform that can be utilized for scaleup and manufacturing of multiple cell therapy products. The concept will use fully-characterized individual equipment modules that can be incorporated in a plug-and-play scenario. Both Dulgar-Tulloch and Bieringer believe this will accelerate the learning curve.

Human cells are fragile

Dealing with living cells as a therapeutic product makes the processes more complex than traditional biotherapeutics. Depending on the therapeutic application, different types of cells must be processed. These cells, which may need to be grown as aggregates, cell suspensions, or single cells, show higher sheer and nutrient and waste sensitivity relative to classical bioproduction cell lines.

In essence, the cells want to “feel good” in the corresponding reactors, which means that they require the right media composition. In addition, oxygen transfer and metabolic stress need to be precisely controlled. To provide the cells the optimal environment both the underlying biological process and the equipment performance must be optimized.

By leveraging both companies’ strengths the joint process team brings together Bayer’s deep knowledge of the biology and the manufacturing requirements of living cells with Cytiva’s expertise in the development of robust and automated equipment solutions. [Dani Serrano/Getty Images]
The development of this user-focused manufacturing platform is intended to address the sensitivity and requirements of different cell systems, work with a variety of model systems comprising different cell types, and utilize a broad range of modeling and lab experimental tools.


Enabling genomic medicines

The collaboration is focused on what the companies envision the entire genomic medicine field needs to bring cell therapies to patients faster. “If we are successful, we believe the entire community of therapy developers, technology providers and most importantly, patients, will benefit from accelerated, cost-effective, and globally available, allogeneic cell therapies,” said Dulgar-Tulloch.

The process began by aligning on the boundary conditions of the platform, i.e., the way to define the modularity (hardware and software plug-and-play), the automation and the process control concept. The initial focus is on two components with a current immense need: a 3D expansion system for production at scale and a robust harvest solution. As additional needs are identified other devices may follow.

The ultimate goal is to gather insights and offer solutions to a wide range of users driving the creation of an allogeneic cell therapy consensus platform. Bieringer emphasized that this will drive economies of scale and simplify global manufacturing, ultimately driving down costs to make allogeneic cell therapies more accessible.

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