Lianne Lelieveldt

Rheumatoid arthritis (RA) is characterized by chronic inflammation in joint tissue. During inflammation, peptidyl arginines are converted to citrullines. Auto-antibodies towards citrullinated proteins are the key factor to sustained inflammation in RA. B-cells producing these anti-citrullinated protein antibodies (ACPAs) are therefore an interesting target for specific therapy. The aim of this study is to selectively target and eliminate these auto-reactive B-cells using a dual-targeting prodrug strategy, which consists of a biologically silenced antigen connected to a cytotoxic drug. The antigen can only bind to the B-cell receptor, and induce cell death, after enzymatic- or chemical activation in close proximity to the B-cell.