Our scientists have found that combining two different immunotherapy drugs, called Abatacept and interleukin-2, can make them more effective and slow down the progress of type 1 diabetes. The findings are an important step towards more licensed immunotherapies, which can tackle the root cause of type 1 diabetes and stop its progression.
Type 1 diabetes develops when the immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas. Immunotherapies are drugs that reprogramme the immune system to stop or weaken this attack.
Abatacept rewriting how we treat type 1
In a historic moment, the first ever immunotherapy drug for type 1 diabetes, called teplizumab, was approved for use in the US last month.
Our scientists are also studying other immunotherapies, which they hope will follow teplizumab’s path to give us a range of different treatments that act on different parts of the type 1 immune attack. This includes a drug called Abatacept, which is already being used to treat people with the autoimmune condition rheumatoid arthritis.
Scientists previously showed that Abatacept can help people newly diagnosed with type 1 diabetes to keep more of their own beta cells for longer, by dampening down the activity of ‘killer’ immune cells that are responsible for destroying healthy beta cells. But Abatacept can also reduce levels of ‘helper’ immune cells, called regulatory T cells, or Tregs.
Tregs are the police of the immune system. They patrol the body and give signals, or immune orders, to the killer immune cells. If Tregs are outnumbered, killer immune cells can break the law and wrongly attack innocent cells in the body. So Abatacept can’t be as effective as it otherwise could be.
A winning combination
Prof Walker and her team wanted to see if they could maximise the benefits, and reduce the unwanted effects, of Abatacept. With our funding, the team treated mice with new-onset type 1 diabetes with a combination of Abatacept and another immunotherapy, called interleukin-2. Interleukin-2 can help to boost levels of Tregs, and is being trialled in children and adults with newly diagnosed type 1 diabetes.
They found that combining Abatacept with interleukin-2 helped the mice to keep the right balance of Tregs. This gives Abatacept a boost by adding an extra level of police protection, helping to stop the criminal damage caused by killer T cells. Mice treated with the combination therapy had more surviving beta cells and lower blood sugar levels compared to mice just treated with one immunotherapy only or those who weren’t given any treatments.
These early-stage results are exciting and could lead to new clinical trials in people with type 1 diabetes. The next steps for Prof Walker’s Diabetes UK-funded project are looking to see if there are any biological signals in mice that could help scientists predict who is likely to benefit most from the combination treatment.
Professor Walker said:
Abatacept has been trialled in people with type 1 diabetes, but the benefit was fairly limited and some individuals did not respond. Our work suggests that combining it with another therapy can make it work better. The second therapy, interleukin-2, is also being explored in people with type 1 diabetes and it’s exciting to think there may be an unexpected benefit of bringing these two approaches together.
Now more than ever, immunotherapies are an important avenue for researchers to explore. Not only could they delay a diagnosis and slow the progression of type 1 in people at risk or newly diagnosed. But they also hold promise to help people already living with type 1 diabetes when used together with future treatments that aim to replace or rescue beta cells.
