anti-ULBP6 monoclonal antibody 23ME-01473

An Fc effector-enhanced, humanized afucosylated monoclonal antibody directed against the natural-killer group 2, member D receptor protein (NKG2D or KLRK1) ligand UL16-binding protein 6 (ULBP6), with potential immunostimulating and antineoplastic activities. Upon administration, anti-ULBP6 monoclonal antibody 23ME-01473 targets and binds to soluble form of ULBP6, thereby preventing the binding of soluble ULBP6 to NKG2D-expressing immune cells. This enhances the binding of NKG2D-expressing immune cells, including natural killer (NK) cells and subset of T cells, to ULBP6-expressing tumor cells, which leads to the activation of NK cells and T cells, the secretion of interferon-gamma (IFNg), and the lysis of tumor cells. In addition, the afucosylated Fc domain of 23ME-01473 binds to the activating Fc receptor low affinity immunoglobulin gamma Fc region receptor III-A (FcgammaRIIIA; CD16a) expressed on NK cells, which enhances antitumor response through antibody-dependent cell-mediated cytotoxicity (ADCC). ULBP6 is a stress-induced cell surface NKG2D ligand overexpressed on cancer cells. The shedding of ULBP6 from tumor cell surface to produce the soluble form allows tumor cells to evade NKG2D-expressing immune cells. 23ME-01473 also targets and binds to ULBP2 and ULBP5, blocking their interaction with NKG2D.