Autologous and allogeneic CAR-T therapies continue to hold significant promise for patients. But with that potential comes challenges, as more CAR-T therapies enter clinical trials and commercialization. Some are universal to both autologous CAR-T and allogeneic CAR-T, but each has its unique obstacles, too.
Abby McDonald, PhD, supervises the Solutions Development team for Be The Match BioTherapies®, a team of professionals who design and implement solutions for cell and gene therapy developers. Our solutions development specialists collaborate with clients to provide access to the proven infrastructure and systems used to manage more than 6,200 cell therapies each year by our parent company, the National Marrow Donor Program® (NMDP)/Be The Match®. By leveraging this world-renowned expertise, Abby and her team help to accelerate patient access to next-generation life-saving cell and gene therapies.
Abby started her career at NMDP/Be The Match as an immunogenetic specialist performing unrelated donor and cord blood searches for patients in need of an allogeneic hematopoietic stem cell transplant. We sat down with her to discuss the challenges facing the CAR-T industry and solutions for overcoming some of those hurdles.
Q: In your time with Be The Match BioTherapies, you’ve designed solutions for many cell and gene therapy companies developing autologous and allogeneic CAR-T therapies. What are the biggest challenges the CAR-T industry is facing today?
A: For both autologous and allogeneic CAR-T therapies, one of the biggest concerns is manufacturing availability. There are only so many slots available within contract manufacturing organizations (CMOs), which creates a significant bottleneck when you’re talking about personalized autologous and allogeneic therapies.
What’s fascinating is that in order to try to overcome the bottleneck, many cell and gene therapy companies have started building their own manufacturing facilities. But this is leading to a new concern: significant competition for experienced, qualified manufacturing staff.
It will be interesting for the market to see how the cell and gene therapy companies and CMOs strike the right balance and don’t create unintended consequences.
Q: Beyond manufacturing, does the inherent variability in human biology play a factor for autologous and allogeneic CAR-T therapies?
A: Absolutely. It’s not like producing a traditional pharmaceutical where there is a specific formula used to create a medication. Every person’s biology is different, which leads to different effectiveness rates for a CAR-T therapy.
Even if two patients for an autologous CAR-T therapy or two healthy donors for an allogeneic CAR-T therapy look the same on paper, the effectiveness of the CAR-T therapy can still be different. That’s why gathering long-term outcomes data in a database like the CIBMTR® Cellular Therapy Registry will be so important. As more patients receive these therapies and we get more data, we can hopefully gain a better understanding of what translates into positive clinical results for patients.
Q: What are the biggest challenges for autologous CAR-T therapies?
A: For autologous CAR-T therapies, I think one of the biggest challenges really circles back to manufacturing availability. You have to manage the patient’s health and disease status against manufacturing slot availability so you can time the collection appropriately. That’s especially critical when the starting material is shipping fresh and not frozen.
Q: Are there challenges specific to allogeneic CAR-T therapies?
A: For allogeneic CAR-Ts, there is broad diversity among healthy donors, and the industry hasn’t identified a truly universal donor. Cell and gene therapy companies have to find donors who have the specific attributes needed for the therapy being developed. Those donors may or may not be willing to donate for a cell therapy, like an allogeneic CAR-T.
On the other hand, some donors may feel more directly connected because their cells could be used to treat a diverse set of patient indications, and they might have a closer connection to one of those indications.
Q: How can the cell and gene therapy industry overcome these barriers impacting the advancement of allogeneic and autologous CAR-T therapies?
A: Standardization is going to be critical in overcoming some of these challenges. While you can’t control human biology, you can control certain aspects of an apheresis collection and manufacturing.
Be The Match BioTherapies is really on the forefront of pushing for standardization in the industry where it makes sense. We understand there are things you can’t standardize. But, there absolutely are things that you can and should standardize, not just for the benefit of one cell and gene therapy company’s product, but for the benefit of all the stakeholders involved with the development of the therapy for the patient.
The cell and gene therapy industry can also rely on experienced partners to help them overcome some of the challenges in developing CAR-T therapies. I talk a lot about “not borrowing worry if it’s not your worry to have.” Therapy developers are experts in developing new, cutting-edge cell and gene therapies. But others are experts in transporting and delivering therapies, finding the right donors and working with payers, just to give a few examples.
That’s a big reason Be The Match BioTherapies exists. We have expertise in all of these areas through 30 years of experience in managing allogeneic hematopoietic stem cell transplants, which is still the most widely used life-saving cell therapy globally.
For example, when Be The Match BioTherapies can help manage the autologous or allogeneic CAR-T supply chain for these companies, help take care of logistics, help make sure all of the dates are scheduled for apheresis and manufacturing, help negotiate those schedules against each other for these companies, that’s one less thing for the cell and gene therapy companies to worry about. We can take the burden on so they can spend that effort elsewhere where they truly have the most expertise in that field.
From an allogeneic CAR-T perspective, when you’re looking to source donors, Be The Match BioTherapies and the NMDP/Be The Match have extensive experience in that area. We have the world’s largest and most diverse registry of highly characterized donors. We have highly trained staff who are very skilled at contacting and educating the donors on what we might be asking them to do, and then consenting the donors appropriately for the intended use of their donation. We conduct a rigorous health history screening and ensure the donor is healthy enough to donate.
There are many steps that need to occur prior to the allogeneic donor’s collection, and our team is extensively trained in all of them. It’s another worry we take on for the cell and gene therapy companies to help them overcome the challenges before collection.
Q: What are you most excited about when it comes to the cell and gene therapy field?
A: What’s really exciting is the idea that patients and their physicians will have multiple potential treatment paths forward to best treat their disease. Their options might not only be hematopoietic stem cell transplant, but autologous CAR-T or allogenic CAR-T or another cell or gene therapy that’s in development today.
I am so excited for our patients to be able to get the best treatment to have the best outcome and the best chance at having additional, high-quality years to live. And to be able to play a role in that—it’s incredibly rewarding.
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