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B7‐H3 is highly overexpressed in a variety of human clinical tumors, and its expression is significantly associated with poor outcomes. In our study, we aimed to develop new antitumor  mA bs by employing cancer cell immunization, and succeeded in generating a mouse anti‐human B7‐H3 antibody (M30) that shows antitumor activity. M30 was humanized (Hu‐M30), and an afucosylated Hu‐M30 ( DS ‐5573a) was also generated. To assess the potency of  DS ‐5573a as a therapeutic  mA b, we characterized this  mA b and evaluated its antitumor activity  in vitro  and  in vivo . Flow cytometry analysis showed that B7‐H3 proteins were expressed on various types of cancer cell lines broadly, and  DS ‐5573a binds to IgC1 and IgC2 domains of human B7‐H3. Antibody‐dependent cellular cytotoxicity activity of  DS ‐5573a was drastically enhanced against medium to high B7‐H3‐expressing cancer cell lines  MDA ‐ MB ‐231 and  NCI ‐H322.  DS ‐5573a also induced high antibody‐dependent cellular cytotoxicity activity against low B7‐H3‐expressing cancer cell line  COLO 205, whereas Hu‐M30 induced little activity against it. In addition,  DS ‐5573a was found to be a novel anti‐B7‐H3 antibody which showed antibody‐dependent cellular phagocytosis activity. Furthermore,  DS ‐5573a showed dose‐dependent and significant antitumor efficacy (0.03–3 mg/kg) in  MDA ‐ MB ‐231‐bearing  SCID  mice (which have functional natural killer cells and macrophages), but little antitumor efficacy in  NOG  mice (which lack natural killer cells and have reduced macrophage function). These results suggest that antitumor activity of  DS ‐5573a is mediated by effector cells, and this  mA b could be a promising antitumor therapy for patients with a wide range of B7‐H3‐expressing tumors.

Development of DS ‐5573a: A novel afucosylated mA b directed at B7‐H3 with potent antitumor activity