Turning the body's attackers into guardians: ToleriGen, a precision cell therapy for Multiple Sclerosis

Federico Fondelli.

Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Spain.

In multiple sclerosis, T cells destroy the myelin that insulates nerve fibres in the brain and spinal cord, leading to severe and progressive disability. Current treatments only work by suppressing the whole immune system, causing serious side effects. This project aims to cure multiple sclerosis by restoring T cell tolerance to myelin rather than switching off the entire immune system.

Our solution takes the T cells that attack myelin and turns them into regulatory T cells (Tregs) that protect it, using tolerogenic dendritic cells from the same patient. To do so, we developed a GMP-compatible protocol able to generate high yields of antigen-specific, suppressive and stable Tregs without the need of genetic engineering. In parallel, we identified a specific pool of myelin peptides covering 58 % of MS patients, allowing us to screen and preselect the patients most likely to respond before production starts. Finally, we developed a genetic test able to predict already in the early days of GMP production whether the batch will be successful.

This approach could replace lifetime broad immune suppression with a more precise treatment that re-educates the immune system itself, reducing infections and side effects in people with multiple sclerosis. Because our method can be directed towards different tissues by simply changing the peptide pool, it could potentially be adapted to other autoimmune diseases like Type 1 Diabetes and Rheumatoid Arthritis.

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