The humanised antibody Alemtuzumab targets the CD52 antigen expressed on T- and B-cells, monocytes and macrophages (white blood cells). It is also expressed on natural killer (NK)-cells, however, its level of expression is lower on these cells. Alemtuzumab has been used since 1991 for the treatment of multiple sclerosis (MS) at Addenbrooke’s Hospital, UK. Several multi-centres are currently testing this promising new treatment in relapsing-remitting multiple sclerosis (RRMS). Alemtuzumab treatment leads to rapid and sustained lymphocyte depletion. Lymphocytes start to reconstitute (recover and return towards normal levels) 18 months post-treatment. The effect of Alemtuzumab on the functionality and frequency of NK-cell subsets has not been studied so far.
Several MS treatments impact on the NK-cell status and this study will explore the effect of Alemtuzumab on this subset of cells. Natural Killer cells that have high levels of a marker called CD56, play a role in immunoregulation. There are a lot of these found in the blood of MSers treated with Daclizumab and Interferon-beta and are inversely correlated with disease activity, so the more of these cells that are present the less active is your MS.
More recently, Mitoxantrone, another MS drug, also led to a significant increase of Natural Killer cells. However, whether these alterations are directly involved in the therapeutic treatment effect remains currently unknown. We are just starting to understand how some treatments impact on these important white blood cell subsets, which play a pivotal role in anti-pathogen responses, anti-cancer responses and autoimmunity.
Our immunological laboratory-based study, funded by Genzyme-Sanofi, will assess the Natural Killer-cell status (functionality and frequency of the different types of Natural Killer cells) of MSers who had Alemtuzumab treatment more than a year ago.