Engineered T Cells Show Promise as Effective Preventative for Diabetes

Special immune cells engineered to stop beta cell destruction may be enough to halt type 1 diabetes progression in its tracks

In 2015, Dr. David Rawlings, Director of Seattle Children’s Research Institute’s Center for Immunity and Immunotherapies (bio), published a paper showing how he and his team were able to target a specific receptor on precursor immune cells to transform them into regulatory T cells.

While this may not sound like much on the surface, it has huge implications for people who suffer from autoimmune diseases.

And now, after spending the last five years refining his methods to treat type 1 diabetes specifically, Dr. Rawlings has made huge progress toward what he views as a potential preventative for this life-altering disease.

The Role of T Cells in T1D Development

Before we can understand why Dr. Rawlings’ method for treating diabetes has the potential to be so effective, we first need to understand the process by which type 1 develops.

In a normal, healthy immune system, there is a variety of different categories of cells, all with different functions. T cells are a type of lymphocyte that plays an important role in protecting the body from disease and infection.

While all T cells start out as precursor cells without specific functions, they eventually differentiate into various types of specialized T cells. Effector T cells are responsible for destroying cells within the body that have become infected with a virus or are otherwise diseased. Regulatory T cells, or Tregs, help keep effector T cells in check by limiting those attacks.

In people with type 1 diabetes, something (possibly a virus) triggers effector T cells to begin attacking beta cells in the pancreas. But it is not the effector cells that are compromised in a person predisposed to developing the disease; It is actually the Tregs that do not function correctly.

Without regulatory cells to stop the attack on the pancreatic cells, the effector T cells continue to destroy the beta cells until insulin levels begin to plummet and blood sugar starts to rise.

In theory, if you could activate precursor T cells to become normal, healthy regulatory T cells, then you could stop this destruction in its tracks, preserving some beta-cell function and preventing the disease from taking hold.

This is exactly what Dr. Rawlings and his team have done.

How Engineered T Cells Can Prevent Diabetes

By activating the FOXP3 gene in precursor T cells, the researchers were able to turn these cells into something like normal Tregs. These “edited regulatory-like T cells,” or edTregs, function in very much the same way as natural regulatory T cells, according to the animal and tissue studies the team has completed (you can read that study here).

Over the last few years, the team has been working on the next step necessary to create an effective diabetes treatment.

Introducing activated edTregs into a person’s system doesn’t guarantee the cells will work to deactivate the effector cells destroying insulin-producing beta cells. To get that result, the team had to identify an antigen that would attract the new cells to the pancreas where they are needed.

The team was able to accomplish this by attaching a specific T cell receptor to the surface of the edTregs that guarantees the edTregs target pancreatic cells within the patient.

Looking Ahead to Clinical Trials

Unfortunately, the team is still a long way away from proclaiming they have found a preventative for type 1 diabetes.

While they are hoping to begin human trials in the near future, there are a few things they must accomplish before that can happen. 

First, they must fine-tune the receptor attached to the edTreg to assure the approach works for the greatest number of diabetic patients. Once they have the exact formula figured out, they then have to enhance the manufacturing process to allow them to quickly and easily create these edTreg cells for clinical use.

One great feature of this particular treatment is that it uses precursor T cells taken from the patient themselves. These cells are then turned into activated edTregs and reintroduced into the body. This means no antirejection drugs are needed, but also that each dose must be manufactured specifically for each patient.

Cure or Prevention?

While many have called Dr. Rawlings’ method a potential cure for diabetes, it is important to understand that this method would only be effective in halting the disease in those patients who still have enough active beta cells left.

If introduced early enough into the disease progression, the edTreg cells could theoretically stop beta cell destruction before too many cells have been lost to maintain normal blood sugars. Drawing from other recent revelations about the timeline of beta-cell destruction, we can assume treatment would need to begin before diagnosis or very soon afterward. 

Still, this preventative treatment may open some doors to a true cure for those of us who have been living with the disease long enough to have lost all our functioning beta cells.

By combining an engineered T cell therapy like this one with any of the various beta-cell implantation methods it would be possible to keep these new cells alive without walling them off from the immune system or utilizing immunosuppressants.

Of course, we are still a long way from anything like this becoming a reality. But with Dr. Rawlings continued research and recent funding increase, true diabetes prevention, and potential cure may be just over the horizon.


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