Definition

A human immunoglobulin (Ig) G1 monoclonal antibody directed against the CD25 subunit-interacting domain of the cytokine interleukin-2 (IL-2; IL2), with potential immunomodulatory activity. Upon administration, anti-CD25-IL2 monoclonal antibody AU-007 targets, binds to and blocks the CD25 subunit-interacting domain of IL-2, thereby blocking the binding of IL-2 to the CD25 subunit (IL-2 receptor subunit alpha; IL-2Ralpha) of the human trimeric IL-2 receptor (IL-2R) expressed on the surface of regulatory T lymphocytes (Tregs), thereby inhibiting IL-2Ralpha-mediated Tregs activation. This may prevent Treg-mediated immunosuppression. As the ability of IL-2 to bind to dimeric CD122 (IL-2Rbeta)/CD132 receptor is preserved, AU-007 promotes immune effector activation by IL-2 via IL-2-mediated signaling through the dimeric IL-2R. This may active an anti-tumor immune response against tumor cells through activation of T lymphocytes, natural killer (NK) cells, and NK T cells, thereby killing cancer cells. In addition, by blocking the binding of IL-2 to CD25 expressed on vascular endothelium and smooth muscle cells and subsequent activation, exacerbation of vascular leak syndrome (VLS) is prevented. IL-2 binds to the IL-2R dimeric receptor expressed on CD8 T effector cells, memory T cells, NK cells and NKT cells and is composed of CD122 and CD132. The IL-2R trimeric receptor expressed on Tregs and vascular endothelium is composed of CD25, CD122 and CD132.