Immune mechanisms of new therapeutic strategies in multiple sclerosis—A focus on alemtuzumab

Alemtuzumab is a humanized monoclonal antibody targeting CD52, a broadly expressed cell surface molecule on immune cells. Application results in a rapid and long-lasting removal of lymphocyte populations from the circulation. Alemtuzumab-treatment of MS patients with relapsing–remitting forms of the disease significantly reduced the risk of relapse and accumulation of disability compared to interferon β-1a treatment in a phase II trial. Interestingly, further analysis together with parallel experimental studies suggested that alemtuzumab not only reduces disease activity due to its immune cell-depleting effect, but also confers neuroprotective effects, presumably by inducing production of neurotrophic factors in autoreactive T cells. However, alemtuzumab-treated MS patients experienced increased rates of novel autoimmunity and a slight increase in infections, demonstrating that alemtuzumab-mediated skewing of the immune cell compartment has a broad influence on immune functions. This review discusses the current concepts about the underlying mechanisms causing these altered immune responses in alemtuzumab-treated MS patients.

► Alemtuzumab is a monoclonal antibody against human CD52.
► Alemtuzumab is highly effective in reducing disease severity in RRMS.
► Alemtuzumab induces long-lasting immune cell depletion via ADCC.
► Alemtuzumab treatment is associated with overt novel autoimmunity.