Poland’s breakthrough in diabetes on a par with the discovery of insulin. “These people may never develop the disease”

Katarzyna Pinkosz, Wprost: The vaccine against type 1 diabetes developed by your team and the company Poltreg has recently received an American patent. Are we getting closer to a breakthrough in type 1 diabetes? What’s more: will we have a “Polish vaccine” against diabetes?

Prof. Piotr Trzonkowski: The vaccine is already there, but still in clinical trials. We can also partially administer it, in a limited way, at the University Clinical Center in Gdańsk under the so-called hospital exception. The patent you mention is one of our several patents for this indication, the second in the United States alone. The project is constantly developing, going through subsequent phases.

Does this mean there’s a simple path to registration?

The patent proceedings in the States have been going on for several years. If we have already obtained authorization, meaning that we obtain permission to offer our vaccine widely, we will have priority when it comes to registration. We are doing everything to make it happen as soon as possible. The realistic perspective for us is 4-5 years. Our diabetes vaccine is evolving.

What does it mean?

We started by giving it to patients with early symptoms of type 1 diabetes. From the point of view of the disease, these are very advanced patients: most of their pancreatic cells are already destroyed.

There is now a trend worldwide to look for patients as early as possible: they can be diagnosed even 5-6 years before the first symptoms of type 1 diabetes appear. Then the use of such a vaccine is much more effective: most of the pancreas is not yet destroyed, we are able to protect it almost completely. Perhaps such people will never be patients, that is: they will never have symptoms of the disease.

We are currently starting a study to give the vaccine to children who would develop diabetes in 5-10 years. Perhaps, thanks to the vaccine, they will never get it.

We talk about a “vaccine” but these are really T-regulatory cells. How do they work?

T-regulatory cells (TREG) are a small population of lymphocytes in our body that ensure that the immune system correctly distinguishes our own tissues from foreign ones and destroys the latter. Each of us has T-reg cells. They protect against autoimmune diseases. Our immune system is an “army” that must be guarded, because if it is not, instead of fighting infections, it starts fighting our own tissues. When it attacks the pancreas, it leads to an autoimmune disease – type 1 diabetes; when it attacks the nervous system – multiple sclerosis appears; when it attacks the joints – rheumatoid arthritis. There are about 70-80 diseases that arise from an autoimmune mechanism.

T-regulatory cells are a kind of policeman that makes sure that our immune system fights the enemy, bacteria, viruses, but does not destroy our own tissues.

The idea of ​​our vaccine is that in patients with autoimmune diseases – because for some reason they do not have T-regulatory cells, or they have too few of them – we take them, multiply them, and then administer them to “tame” the immune system. This is how our vaccine works. When in type 1 diabetes the immune system destroys the pancreas, administering immune cells causes the immune system to stop working in this way.

What is the effect of using T-reg cells?

The effect depends on when we administer them. If the patient already has symptoms of diabetes, then most of the pancreas is already destroyed (approx. 70%), we can only weaken the development of symptoms. If it is still in the pre-symptomatic period, 5-10 years before the symptoms appear, then the immune system has not yet destroyed the pancreas; there is something to fight for.

Can we already say who will develop type 1 diabetes in a few years?

In some countries, there are already programs for early detection of type 1 diabetes. Last year, the Italian parliament passed a law that all children at school should undergo screening tests to see if they are at risk of developing type 1 diabetes. In Poland, we cooperate with Prof. Artur Bossowski from the Medical University of Białystok, who is conducting such pilot studies in Podlasie. It turns out that 3.5% of primary school students are at risk, i.e. they will potentially develop type 1 diabetes. Over 3,000 students have already been tested.

3.5% of children at risk of type 1 diabetes is a lot. When should such tests be performed? Some children get sick in the first years of life.

It’s a difficult issue. In Italy, testing is done at school age, but in the States, for example, a child can get tested every now and then. We’re really just starting epidemiological programs, we don’t know yet when it’s best to do such testing.

T-reg cells are the patient’s cells – so this drug will have to be made individually for each one?

For now, yes, but in the future – not necessarily. In the dossier of the company that produces T-reg cells, we also have an allogeneic approach: we take cells from a healthy donor and prepare them so that they can be used in other patients. This is much more difficult, we are still at the preclinical stage, but perhaps in the future it will be possible to create such a treatment.

We currently have many different products based on T-regulatory cells. Two indications have drugs already in clinical trials; we have three more drug candidates in preclinical trials, and we will probably enter clinical trials with them soon.

Apart from type 1 diabetes, what other diseases can T-reg cells be used in?

We have about 70-80 different autoimmune diseases. In each of them we could find a place for such a treatment. We are conducting clinical trials in the treatment of type 1 diabetes and in multiple sclerosis: these two diseases are our priority because they are among the most common autoimmune diseases. It is a big challenge.

You are not the only team in the world working on such a solution. What are the chances that this therapy invented in Poland will be introduced?

We have the longest clinical trials and the longest experience. When we were preparing for the clinical trials leading to authorization, we received information from the European Medicines Agency that we could consider it if we were able to provide the results of a safety study of this therapy at least 5 years after administration. We recently announced the results in patients 7-12 years after the administration of cells: they continue to secrete insulin, and the therapy is safe. No one else has the results of such long-term observations.

How did you come up with the idea to use T-reg cells for treatment?

I did my PhD on the effectiveness of vaccinations in the elderly. I noticed that if T-regulatory cells accumulate in the elderly, vaccinations are much less effective. We observed the effect of inhibiting immunity using T-regulatory cells. During in vitro studies, we confirmed that regulatory cells have this potential. At the same time, we also studied graft-versus-host disease – in patients after a bone marrow transplant, the transplanted bone marrow begins to recognize the patient as someone foreign and destroys him; the disease is very often fatal. We noticed that these patients often have too few T-regulatory cells. We injected them with them: this caused the disease to subside: the symptoms receded, and other drugs could be withdrawn. This was confirmation that T-regulatory cells may have therapeutic potential.

Around 2008-9 I met with Professor Małgorzata Myśliwiec and Dr. Natalia Marek-Trzonkowska, who is now my wife and a professor, and who were researching type 1 diabetes. It turned out that the occurrence of the disease also correlates with the lack of T-regulatory lymphocytes. We tried to use T-regulatory cells in diabetes as well. This is where the next research began.

Is collaboration between scientists and clinicians important?

It is absolutely necessary. Listening to another person who has a different baggage of experience and knowledge gives rise to such discoveries.

At first, it was an academic study, we wanted to produce T-reg cells ourselves, we were guided by scientific curiosity. We are currently talking about a partnership, part of our portfolio was created in cooperation with an American company. We are talking about commercializing the vaccine not only in Poland, but all over the world. To have a chance of commercialization, we have to talk to world leaders. We started with one drug, now there are more of them, we are educating a team, thanks to which a delicate network of connections is being created, which is causing the biotechnology industry in Poland to start functioning better and better.

Are T-reg cells actually a drug or a vaccine?

A medicine – or rather a product of advanced therapy. Poland should invest in such technologies; they will certainly be cheaper then, because it will not be necessary to buy a license from abroad.

Are these cells a chance not only for diabetics but also for other patients with autoimmune diseases?

If we had money and more hands to work, tomorrow we would probably start producing not only drugs for diabetes and multiple sclerosis, but also for rheumatoid arthritis, inflammatory bowel disease, autoinflammatory skin diseases, severe asthma, organ transplant rejection and graft-versus-host disease.

2024 has been declared the year of autoimmune diseases. It can be said that this is the last unmet medical need. Very often in cancers we are able to offer effective drugs, and in autoimmune diseases – only therapies that alleviate symptoms, but do not particularly modify the course of the disease itself. Cell therapies are hope for patients. We would very much like to fulfill these hopes.

T-reg cells can also be effective in neurodegenerative diseases, such as amyotrophic lateral sclerosis. They also have regenerative properties, so the possibilities for their use are really very large. Let’s just hope we have enough hands and opportunities to try to use them in each of these indications.