TIPPDECRA · Tolerogenic immunotherapy with peptide-pulsed dendritic cells in rheumatoid arthritis

Tolerogenic immunotherapy with peptide-pulsed dendritic cells in rheumatoid arthritis

Rheumatoid arthritis (RA) is a disabling and painful disease of the joints. It affects roughly 1 in 400 people world-wide; but in certain regions (Western Europe, North America) it can affect as many as 1 in 160 females. Globally, RA has been ranked as the 42nd highest contributor to disability (out of 291 conditions) – just below malaria. RA is caused by the patient’s own immune system attacking the joints. Although current treatments can be effective at alleviating symptoms they do not provide a cure and the associated general immunosuppression can cause unwanted side effects. We previously developed a new treatment aiming to restrain the immune attack on the joints long-term. The idea behind this new treatment is that the patient’s immune system can be re-educated so that the immune attacks come to a halt, i.e. the immune system becomes tolerant. This can be achieved by treatment with so-called tolerogenic dendritic cells (tolDC). We have developed a robust method to generate these tolDC from the blood of RA patients and subsequently inject them back into a rheumatic knee joint. We recently completed a phase I clinical trial with these tolDC showing that this new cellular therapy is safe. However, in order to take the next step and conduct further trials to demonstrate that tolDC effectively reduce arthritis, we need to improve the treatment to maximise the likelihood of success. This can be achieved by specifically targeting the tolDC to relevant joint components that we know are being attacked by the immune system in RA patients. For this study we used heat shock proteins (HSP) as the relevant joint specific component. Previous studies have shown that certain heat shock proteins are present in the rheumatic joint and become an easy target for destructive immune attacks. Our goal is to stop these attacks by targeting tolDC to these HSP; this can be achieved by ‘loading’ tolDC with the relevant HSP. The objectives of this research were: 1) to select small, relevant heat shock protein components (called HSP-peptides) that can be loaded onto tolDC 2) to show that these HSP-peptide-loaded tolDC can tolerise immune cells from RA patients 3) to study weather HSP-loaded tolDC are capable of ameliorating disease severity in a mouse model of rheumatoid arthritis

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз