Antitumor activities against breast cancers by an afucosylated anti‐HER2 monoclonal antibody H2Mab‐77‐mG2a‐f

Abstract

AbstractBreast cancer patients with high levels of human epidermal growth factor receptor 2 (HER2) expression have worse clinical outcomes. Anti‐HER2 monoclonal antibody (mAb) is the most important therapeutic modality for HER2‐positive breast cancer. We previously immunized mice with the ectodomain of HER2 to create the anti‐HER2 mAb, H2Mab‐77 (mouse IgG1, kappa). This was then altered to produce H2Mab‐77‐mG2a‐f, an afucosylated mouse IgG2a. In the present work, we examined the reactivity of H2Mab‐77‐mG2a‐f and antitumor effects against breast cancers in vitro and in vivo. BT‐474, an endogenously HER2‐expressing breast cancer cell line, was identified by H2Mab‐77‐mG2a‐f with a strong binding affinity (a dissociation constant [KD]: 5.0 × 10−9 M). H2Mab‐77‐mG2a‐f could stain HER2 of breast cancer tissues in immunohistochemistry and detect HER2 protein in Western blot analysis. Furthermore, H2Mab‐77‐mG2a‐f demonstrated strong antibody‐dependent cellular cytotoxicity (ADCC) and complement‐dependent cytotoxicity (CDC) for BT‐474 cells. MDA‐MB‐468, a HER2‐negative breast cancer cell line, was unaffected by H2Mab‐77‐mG2a‐f. Additionally, in the BT‐474‐bearing tumor xenograft model, H2Mab‐77‐mG2a‐f substantially suppressed tumor development when compared with the control mouse IgG2a mAb. In contrast, the HER2‐negative MDA‐MB‐468‐bearing tumor xenograft model showed no response to H2Mab‐77‐mG2a‐f. These findings point to the possibility of H2Mab‐77‐mG2a‐f as a treatment regimen by showing that it has antitumor effects on HER2‐positive breast tumors.