VivoGenie Anti-Human CD25 (IL-2R) (Daclizumab) - Fc Reduced Biosimilar (IVMB0406)

Interleukin-2 receptor (IL-2R), which regulates normal immune function and is involved in signal transduction, cell growth and survival , is composed of CD25, CD122, and CD132 . CD25 is the alpha-chain of IL-2R and its expression is upregulated in resting T cells after activation, which in turn increases the binding capacity of IL-2 and positively affects signaling for T cell proliferation and survival .

Daclizumab prevents the formation of the heterotrimeric IL-2R and selectively blocks IL-2R-mediated signaling . By masking the IL-2 binding site on IL-2R, daclizumab inhibits T cell activation and proliferation as well as prevents IL-2 from stimulating Tregs to induce apoptosis in effector T cells . Additionally, daclizumab can remove CD25 from the surfaces of T cells via monocyte-dependent trogocytosis (defined as the active transfer of plasma membrane fragments between two live cells triggered by interaction between a cognate antigen on one cell and an antigen receptor signaling pathway on another cell) . Daclizumab also inhibits activation and proliferation of T cells by blocking dendritic cells from presenting IL-2 to resting T cells . Daclizumab reduces T cell CD25 levels via a mechanism that requires Fc domain interaction with FcR on monocytes, but not on natural killer cells .

Blocking IL-2 from binding to T cells leads to increased binding to CD56 ^bright NK cells via the IL-2R beta subunit . This then leads to an expansion of CD56 ^bright NK cells, which target and kill activated T cells and is associated with reduced inflammation in the brain and decreased atrophy of brain tissue.

Daclizumab is humanized anti-Tac and is composed of two humanized gamma-1 heavy chains and two humanized kappa light chains that are sequence optimized for high affinity . Daclizumab has been used in the treatment or prevention of a variety of autoimmune disorders and renal allograft rejection, respectively .