NC762 is a humanized IgG1κ monoclonal antibody that targets human B7-H4 (B7 homolog 4). Its Fc region contains three point mutations (S239D/A330L/I332E; DLE) to enhance binding to CD16a (FcγRIIIa), leading to increased antibody-dependent cellular cytotoxicity (ADCC). By binding to tumor-expressed B7-H4, NC762 inhibits tumor growth in vivo. This compound can be utilized in research on advanced or metastatic solid tumors.

NC762 binds to B7-H4 with an EC50 of 1.12 nM in 624Mel.B7H4 cells and 0.976 nM in SKBR3 cells, within a concentration range of 0.01-100 nM. In human 293T cells, it binds B7-H4 in the range of 0.1 ng/mL-100 μg/mL, but shows no affinity for mouse B7-H4. Compared to V5.hlgG1, NC762 enhances binding to CD16a in a concentration range of 0.1 pM-1000 nM. Additionally, NC762 exhibits ADCC activity in 624Mel.B7H4 and SKBR3 when incubated with Jurkat effector cell lines for 5 hours at concentrations between 0.1-100 pM.

NC762, administered intraperitoneally at doses of (1-30 mg/kg every 7 days for a total of 4 doses) in NSG mice implanted subcutaneously with 1E06 624Mel.hB7H4 cells and 3E05 human PBMCs, reduced tumor volume in a dose-dependent manner. At a dose of (10 mg/kg every 4 days for 7 doses), NC762 demonstrated that NK cells contributed to decreased tumor growth mediated by B7H4 and prolonged survival in NSG mouse models with 1E06 624Mel.hB7H4 cells and either 1E06 total PBMCs or NK cell-depleted PBMCs. In models with 1E06 624Mel.hB7H4 cells and either no PBMCs or human T cells, NC762 (10 mg/kg every 7 days for 4 doses) showed restricted tumor growth in the absence of PBMCs. Furthermore, in NSG mice implanted with 1E06 624Mel.hB7H4 cells, NC762 (10 mg/kg every 7 days for 4 doses) exhibited tumor growth inhibition comparable to that of an NC762 variant with lower Fc affinity, suggesting a mechanism of tumor growth restriction not reliant on ADCC.