Project ACT series
This article is part of a series exploring the different ways that Breakthrough T1D’s Project ACT (Accelerate Cell Therapies) will shape the future of cell therapies for type 1 diabetes (T1D). The next article in the series will discuss the progress of cell therapies in clinical trials.
We’ve made major progress in the development of cell replacement therapies for type 1 diabetes (T1D) over the past couple of decades. We know that manufactured islets, such as Vertex’s VX-880 (now Zimislecel), can restore insulin therapy independence and glucose control when implanted into people with T1D.
However, there is more work to do.
We need to make sure the cells survive and function, ideally without immunosuppression, and ensure that these therapies are accessible to everyone with T1D. Read on to learn more about where there’s room for improvement and what we’re doing about it.
Optimizing manufactured islets
Priority #1: Cell source
Current external cell sources that are not manufactured in the lab, such as those from deceased donor pancreases or a person’s own cells, are in extremely limited supply. The only FDA-approved cell therapy for T1D, Lantidra®, requires donor cells, and it can take up to three pancreases to get enough islets for one transplant. This is unsustainable and limits the number of people who can get this therapy.
We can consistently generate an unlimited source of islet cells in the lab. This way, we can make enough insulin-producing cells for everyone with T1D and have a single cell source to test and compare multiple strategies to protect them.
Breakthrough T1D is funding an initiative at the Advanced Regenerative Manufacturing Institute (ARMI) to scale up Dr. Jeffrey Millman’s protocol to generate unlimited manufactured islets in a reliable, automated, and reproducible way. Breakthrough T1D is also building a partnership with the Cedars-Sinai Biomanufacturing Center to accomplish this goal.
Priority #2: Cell survival
Implanted islets that move through the bloodstream can cause an inflammatory reaction, resulting in cell death. Alternatively, those that are implanted in devices that are cut off from the blood and immune system are unable to get nutrients and oxygen, again leading to cell death.
It doesn’t have to be the pancreas, but islets need access to nutrients and oxygen so that they can survive for long periods of time and produce insulin.
Breakthrough T1D is funding research to develop scaffolds, which are specialized biomaterials that islet cells can stick to and get nutrients and oxygen to help them survive. Similarly, islets implanted in encapsulation devices, such as Sernova’s Cell Pouch™, can access nutrients and oxygen while having the added benefit of being protected from the immune system. There are also various Breakthrough T1D-funded clinical studies that are investigating different places in the body for manufactured islets, including the omentum and abdominal wall.
Omentum
The omentum is a fatty tissue layer that surrounds and protects the organs in your abdomen. Researchers are testing it as a new implantation site for manufactured islets.
Priority #3: Cell protection
Like organ transplants, manufactured islet therapies from an external source are recognized by the immune system as “non-self,” leading to immune rejection. Currently available cell therapies require broad immunosuppressants that may come with unwelcome side effects, including increased risk of infection and malignancy and toxicity to kidneys, nerves, and islet cells themselves.
By swapping standard immunosuppressives with options that have less complications, more people with T1D will be able to access these therapies.
Research and clinical studies funded by Breakthrough T1D approach immune protection from many different angles. This includes genetically engineered islets that can evade immune detection, encapsulation devices, and immunomodulatory therapeutics that can dampen the immune response.
The future of manufactured islets and T1D cures
There’s a lot of promising solutions in the pipeline. What’s next? Unlocking access.
“We recognize that approval of cures is not a life-changing breakthrough if people do not have access to the therapy itself,” said Aaron Turner-Phifer, Senior Director of Health Policy at Breakthrough T1D. “Building on the experience gained from past breakthroughs, we are working now, across our Mission teams, to identify and remove any potential barriers to people accessing cell therapies.”
“While our work is just beginning, we’ve already conducted market analysis to identify clinical and payer barriers to give us clarity on where to start. We are directly engaging policymakers and health plans to educate them on T1D cell therapies. We’ve also launched data projects to begin to generate the types of data required to positively inform future policy and coverage decisions.”
Aaron Turner-Phifer
In the coming years, it’s likely that first-generation manufactured islet therapies will be available to people with T1D with severe hypoglycemia unawareness and will require broad immunosuppression.
Later, advancements in cell survival and immune protection—combined with the advent of more tolerable immune suppression approaches—will open the doors for more people with T1D to access these life-changing therapies.
Project ACT
Scientific progress takes time, money, and effort. To accelerate islet replacement therapies faster than ever, Breakthrough T1D launched Project ACT (Accelerate Cell Therapies) to simultaneously advance research, development, regulatory policies, access, and adoption of manufactured islet therapies that do not require broad immunosuppression.
Without continuous support from the T1D community and its supporters, we would never have gotten this far. Breakthrough T1D looks forward to a future where manufactured islet therapies are a reality for everyone with T1D, and we will not stop until we get there.
