Why the Time Is Now for Allogeneic Cell Therapies
Why do we need allogeneic therapies when autologous therapies have enjoyed such success?
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The following article is an opinion piece written by Andrew Schulman. The views and opinions expressed in this article are those of the author and do not necessarily reflect the official position of Technology Networks.
The lessons learned from the development and manufacture of autologous cell therapies are helping lay a solid groundwork for the high potential and exciting field of allogeneic cell therapies. While the world focused on creating and distributing COVID-19 vaccines, a segment of the biotech industry kept pushing for the future generation of cell therapies. Now, the combination of lessons learned, momentum, and collaborative spirit will help this field become successful.
A series of market moves coupled with news from clinical trials point to increasing momentum and desire to see allogeneic therapies get to patients. Bayer is gearing up to manufacture its first allogeneic cell therapy and is far from the only big pharma company expanding into this promising area. In January 2023, Bristol Myers Squibb started the construction of its first European CAR T-cell therapy production center at the Leiden Bio Science Park. According to the Alliance for Regenerative Medicine, there were more than 500 cell therapy clinical trials underway globally in 2023.
But why do we need allogeneic therapies when autologous therapies have enjoyed such success?
It’s our belief that while both autologous and allogeneic therapies have an important role to play in patient treatment at least for the next decade, there are some subtle differences that make allogeneic therapies a particularly attractive proposition.
Rather than being developed as a bespoke treatment using the patient’s own cells, allogeneic therapies use cells from healthy donors, which are developed as off-the-shelf treatments for many types of patients making them less costly to manufacture.
Additionally, a combination of autologous and allogeneic therapies could offer the best options for treating some patients. For instance, a transient allogeneic therapy could be administered to patients who are too sick to receive autologous therapies, either because their disease is progressing too rapidly or because their cells are not healthy enough to be used in the manufacturing process, followed by a more persistent immunization against the disease via an autologous cell therapy.
Allogeneic therapies represent a more balanced opportunity between a scaled-up, yet personalized, medicine. They also have the potential to reduce the cost of therapy to patients because they are “off-the-shelf”. In addition, allogeneic therapies may be able to address new modalities because the cells can be genetically manipulated depending on the patient’s needs.
Collaboration is essential
Working for global life sciences leader Cytiva, we believe the secret to bringing allogeneic therapies to patients is to form collaborations that enable us to bring different yet complementary skills together. For example, in 2021, we created close ties with Bayer to collaborate on the development of an allogeneic cell therapy manufacturing platform.
This relationship is particularly energizing for us because Bayer is committed to cell therapies, and together we intend to establish new industry standards for manufacturing. A joint global team has defined core requirements and is already prototyping innovative equipment and automation solutions with allogenic cell therapy in mind from the start. We are focusing on manufacturing speed, flexibility and a robust “plug and play” operating environment.
While our collaboration with Bayer focuses on building an allogeneic cell therapy manufacturing platform for large-scale production, together we also see the importance of developing solutions for drug developers at all stages. Part of our focus in building this platform is to find ways that we can help translational groups develop their processes more efficiently, so they can seamlessly transition from early-stage scientific research and development to a manufacturing workflow as their therapies mature. Ultimately, it is going to take this type of collaborative, end-to-end approach to make the promise of allogeneic cell therapy a reality.
Learning from bioprocessing manufacturing
When thinking about ways to scale up the manufacture of allogenic therapies, it is also helpful to draw on the lessons from other therapeutic areas. For example, the manufacturing of monoclonal antibodies (mAbs), which have dominated the biopharmaceutical stage for more than 30 years, has advanced significantly and become more efficient in recent years.
Early on and long before the COVID pandemic, we realized there was a constant and growing need for flexible common designs for mAbs and viral vector manufacturing to reduce development times across the biopharma industry. We decided to take a strategic approach and began working to establish standard platforms for mAbs and viral vector manufacturing. In one case, we developed standardized, single-use, self-contained manifolds that can be adjusted according to the specific requirements of unit operations. This solution provides great flexibility to optimize efficiency through maximization of filter usage and minimization of holdup volume.
Using standardized designs also reduces the need for new validations and aligns with a set list of parts and components that can be pre-ordered to dramatically reduce lead times. For instance, one universal biocontainer bag can be used across the platform (for storage, mixing bioreactor, etc.), further reducing the amount of validation required. Scaling can be further simplified when working with our experts who are experienced using such standardized equipment.
We are now working to “industrialize” allogeneic cell therapies. This “industrialization” effort is a vital undertaking. Using a toolbox approach and single-use consumables allows for quicker, more flexible production. Creating more standard, consistent manufacturing enables increased access to these innovative, life-changing treatments.
Scientists have been working to develop allogenic cell therapies for some time. However, momentum accelerated when drug developers used the experience and knowledge gained from autologous cell therapy clinical trials to better understand how allogenic therapies work. The knowledge gained from the regulatory approvals of CAR-T autologous cell therapies Kymriah and Yescarta contributed to today’s pipeline of allogeneic cell therapies.
In terms of workflow, autologous and allogeneic therapies use virtually the same process to access, isolate and activate T cells and Natural Killer cells (NK, or K cells). The difference comes in the expansion stage, where allogeneic therapies require much more production. This includes handling and processing much larger liquid volumes, treating larger patient pools with a single batch and also achieving complete consistency between batches to ensure the efficacy of treatment and safety profile for the patient.
In addition to the lessons learned from autologous therapies, gene editing has enabled a one-to-many approach that can be applied by allogeneic therapies. Recent technology innovations have enabled increased stability and large therapeutic payloads, including multiple, more complex gene insertions and more consistent and predictable expression.
Some cell therapy innovators are using induced pluripotent stem cells (iPSCs) for a variety of applications, and, as a result, we have a better understanding of the specific characteristics and requirements of those cells. For example, we have increased knowledge of the optimal culture conditions required and are able to design fit-for-purpose cultivation systems. This is crucial considering the fact that iPSCs might become an essential starting material for allogeneic cell therapies in the future based on their unique features such as the ability to be expanded indefinitely and differentiated into any cell type. With iPSCs, multiple genetic edits can be more easily integrated to allow new treatment modalities within the existing immune cell therapy space.
What’s holding us back
With so many ways to get to the destination – increased use of allogeneic therapies – it’s challenging to know what special recipe a biopharma company should pursue. But we need to answer this challenge. Our industry must figure out what type of manufacturing platform is needed to develop and enable future therapeutics. Without the right platform, new therapies won’t succeed. We must work collaboratively with industry leaders and competitors to understand the needs of the industry from pre-clinical research through to commercialization.
Chemistry, Manufacturing & Controls (CMC) remains a bottleneck in bringing allogeneic cell therapies to patients. Allogeneic cell therapies have the potential to provide flexibility for patients and lower costs for manufacturers. As we witnessed with COVID-19, research and translational scientists, (bio)pharma and biotech companies, and regulatory agencies worldwide can make significant progress when we collaborate and focus our resources and actions on achieving a shared goal.
As an industry, we must agree on standard workflow approaches for the manufacture of allogeneic therapies where possible, and we have to be more willing to consider that not everything will be optimized or proven as new indications arise.
Now that the COVID-19 pandemic has been declared to be officially over, it’s time for us to unite as an industry and accelerate the work we do together to drive the development of new therapeutic modalities, especially allogeneic cell therapies, alongside autologous cell therapies. The need for these therapies continues, perhaps with even greater urgency as health providers move out from under the shadow of severe COVID-19 infections and return to addressing a broader population of patients.
About the author:
Andrew Schulman is allogenic strategy manager at Cytiva.