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B7-H3 has been identified as a cell surface protein with limited expression on normal tissues but over-expressed on the epithelium and tumor-associated vasculature in solid tumors. Overexpression of this molecule has been shown to be associated with cancer disease severity, risk of recurrence and reduced survival. The Company's early studies showed that ligation of B7-H3 by select monoclonal antibodies (mAbs) led to mAb internalization and antitumor activity toward B7-H3-expressing tumor cells when conjugated to a toxic payload. Based on these results,
As described in the paper 'Preclinical Development of MGC018, a Duocarmycin-based Antibody-drug Conjugate Targeting B7-H3 for Solid Cancer,' the authors report on preclinical studies that showed that MGC018 mediated specific in vitro killing across a range of B7-H3-expressing solid tumor cell types. Furthermore, the preclinical studies showed that MGC018 mediated bystander in vitro killing of B7-H3-negative tumor cells in the presence of B7-H3-positive tumor cells.
MGC018 displayed potent antitumor activity in preclinical tumor xenograft models of breast, ovarian and lung cancer, as well as melanoma. Additionally, antitumor activity was observed toward patient-derived tumor xenograft models of breast, prostate and head and neck cancer displaying heterogeneous expression of B7-H3. Importantly, MGC018 exhibited an acceptable pharmacokinetic and safety profile in cynomolgus monkeys following repeat-dose administration.
'With its overexpression on a wide range of solid cancers but limited presence on normal tissues, B7-H3 is an attractive candidate for an ADC-targeting approach,' said
About MGC018
MGC018 is comprised of an anti-B7-H3 humanized IgG1/kappa monoclonal antibody conjugated via a cleavable linker to the prodrug seco-DUocarmycin hydroxyBenzamide Azaindole (DUBA; licensed from
About
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