Daclizumab Therapy for Multiple Sclerosis

Daclizumab is a humanized monoclonal antibody that prevents formation of high-affinity interleukin (IL)-2 receptor (IL-2R). Because activated T cells up-regulate high-affinity IL-2R and IL-2 is used to grow activated T cells in vitro, daclizumab was envisioned to selectively inhibit activated T cells. However, the mechanism of action (MOA) of daclizumab is surprisingly broad and it includes many unanticipated effects on innate immunity. Specifically, daclizumab modulates the development of innate lymphoid cells, leading to expansion of immunoregulatory CD56^bright natural killer (NK) cells. Activated CD56^bright NK cells migrate to the intrathecal compartment in multiple sclerosis (MS) and regulate autoreactive T cells via cytotoxicity. Finally, daclizumab also restricts initial steps of T-cell activation by blocking trans-presentation of IL-2 by dendritic cells to antigen-specific T cells. In conclusion, daclizumab has complex immunomodulatory effects with resultant inhibition of central nervous system inflammation in MS.