Autologous Tolerogenic Dendritic Cells for Rheumatoid Arthritis (AuToDeCRA)
Currently we rely on general dampening of immune responses (immunosuppression). At best, these approaches lead to symptom control, but they do not address the underlying cause and often carry risks of serious infection.
What we did
We developed a new treatment that uses a patient’s own immune cells, carefully manipulated in the laboratory. By delivering them back into the same individual our ambition is that they might correct (‘tolerise’) the disrupted immune system without associated immunosuppression. We called these cells tolerogenic dendritic cells (tolDC). We developed tolDC therapy from initial concept, extensive testing in the laboratory through to translation into a clinical-grade product fit for injection into patients. We performed a first-in-human safety study of our therapy (a phase 1 clinical trial), which was successful.
Who was involved?
This was a huge team effort. The trial itself involved scientists, the Newcastle Advanced Therapies Unit, rheumatologists, lab technicians, trialists and statisticians. Throughout the twelve-year journey from concept to completion, we relied on close partnerships with Patient Partners (E.g. for protocol development) as well as the Rheumatology Department and the Clinical Research Facility at Newcastle Hospitals.
What was the output and why is this significant?
Our data show injecting tolDCs into inflamed joints did not induce disease worsening and appeared safe. It was also well tolerated by participants. Safety is the most important outcome for a phase 1 clinical study and paves the way for downstream studies investigating other outcomes of interest.
What are the next steps?
We are now preparing for AuToDeCRA 2. In this study we will compare different routes of tolDC administration, which is another key question for cellular therapies. We will also look for direct effects of tolDC treatment on the disrupted immune system by taking samples (e.g. blood) from patients before and after treatment. We will perform in-depth analyses on the immune cells in these samples to understand how tolDC have changed their behaviour. If we can demonstrate a definite beneficial effect of tolDC therapy on the immune system, this will be a major stimulus for progression to larger trials, even testing whether the approach could prevent early RA from becoming chronic.
Reference:  Bell G et al. Ann Rheum Dis 2015(76:227-34)