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ERC grants for research on diabetes and immunotherapy

Filipe Pereira and Charlotte Ling
Filipe Pereira and Charlotte Ling

Two innovation-driven research projects at Lund University have been awarded a Proof of Concept Grant by the European Research Council, ERC. They relate to biomarkers for predicting who benefits from metformin in the treatment of type 2 diabetes and new technology to enable powerful and focused therapies for the treatment of solid tumours.

Charlotte Ling has been awarded an ERC Proof of Concept Grant for the further development of successful research into epigenetics and biomarkers. In her research, she predicts which patients with type 2 diabetes are likely to benefit from treatment with metformin, and which should be given another medicine.
Charlotte Ling is a professor of diabetes research and a pioneer in the research field of epigenetics and diabetes. In 2016, she received an ERC Consolidator Grant of SEK 20 million, focused on developing a new method for predicting, preventing and treating type 2 diabetes. A couple of years later, she and her colleagues published new observations in Science Translational Medicine – the discovery of a combination of epigenetic biomarkers that can, using a blood test, predict which individuals with type 2 diabetes will benefit from the regularly prescribed medicine metformin, which of them will not respond to the treatment and which of them are highly likely to suffer side-effects.

“Thirty per cent of those with type 2 diabetes do not respond to treatment with metformin, which is the most common medicine used to lower blood sugar. Five to ten per cent of them suffer serious side effects in the form of stomach and intestinal problems. So, there is a great need to personalise care by being able to establish early in the treatment process who will be helped by the medication and who is to be prescribed other medicine. Our study identified blood-borne epigenetic biomarkers that can be used for this,” says Charlotte Ling.

Three population studies* formed the basis of this discovery. By measuring DNA methylation markers** in the blood cells of participants before they commenced treatment, researchers were able to discover an epigenetic pattern, a combination of biomarkers that showed who responded well and who did not respond to treatment with metformin.

The discovery was patented in 2018, and even if there was interest in the innovation from potential purchasers, the researchers have set their sights on a follow-up study to test the biomarkers in larger cohorts, validating and replicating the results. Charlotte Ling has now received the ERC Proof of Concept Grant to further develop the results of research from 2018 and to investigate the innovation’s potential.

“We wish to optimise the biomarkers and now, in collaboration with researchers in Uppsala, we are conducting a randomised study in which patients receive metformin or SGLT2 inhibitors. Our aim is to develop a test kit that can be used in healthcare in order to find out which patients will benefit from metformin treatment,” says Charlotte Ling.

The extensive work to include at least 500 people in a validation cohort and to complete the randomised study starts now.

Since he received the ERC Consolidator Grant for the development of new strategies for immunotherapies in 2019, Filipe Pereira has come a long way. To say the least. One of the goals three years ago was to understand what drives the specialisation of dendritic cells. He has now received the ERC Proof of Concept Grant, in order to exploit reprogrammed tumour cells to identify tumour antigens.

“The dendritic cells play an important role in the immune system, since they track down foreign substances in the body such as tumour cells and present them as antigens for the body’s natural killer cells. This tells the natural killer cells which invaders to attack,” says Filipe Pereira, professor of molecular medicine.

Immunotherapy is one way of getting the body’s own immune defences to recognise and attack the cancer cells. For each type of cancer, a number of genetic mutations occur, resulting in specific tumour antigens being produced. Since they are unique to each tumour and patient, they make ideal molecular targets.

“But there is no efficient way at present to identify these special tumour antigens, and as a result immunotherapy has had limited success. There is a need to develop new technology that enables powerful, focused therapies for treating solid tumours.”

Filipe Pereira’s research team have previously identified a combination of three proteins that have made it possible to re-programme human skin cells into dendritic cells. The next step was a to prepare a viral vector with three different re-programming genes. The viral vector then transported the selected genes to the tumour cell, which was re-programmed to a dendritic cell as a result. Filipe Pereira calls the technique Trojan DC, since just like the Trojan Horse, it conceals its warriors within, only to defeat the enemy from the inside. The re-programming of tumour cells technique opens the possibility of being able to identify patient and tumour specific antigens that can summon an immune response.
“Through the research project, which we call NeoIDC, we hope to be able to start a new company, in order to completely explore the platform for antigen identification. We think that this is the path to the next generation of antigen-based cancer vaccines and tailored immunotherapies,” concludes Filipe Pereira.