Antitumor activities against breast cancers by an afucosylated anti-HER2 monoclonal antibody H 2 Mab-77-mG 2a -f.

Breast 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, H 2 Mab-77 (mouse IgG 1 , kappa). This was then altered to produce H 2 Mab-77-mG 2a -f, an afucosylated mouse IgG 2a . In the present work, we examined the reactivity of H 2 Mab-77-mG 2a -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 H 2 Mab-77-mG 2a -f with a strong binding affinity (a dissociation constant [K D ]: 5.0 × 10 -9  M). H 2 Mab-77-mG 2a -f could stain HER2 of breast cancer tissues in immunohistochemistry and detect HER2 protein in Western blot analysis. Furthermore, H 2 Mab-77-mG 2a -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 H 2 Mab-77-mG 2a -f. Additionally, in the BT-474-bearing tumor xenograft model, H 2 Mab-77-mG 2a -f substantially suppressed tumor development when compared with the control mouse IgG 2a mAb. In contrast, the HER2-negative MDA-MB-468-bearing tumor xenograft model showed no response to H 2 Mab-77-mG 2a -f. These findings point to the possibility of H 2 Mab-77-mG 2a -f as a treatment regimen by showing that it has antitumor effects on HER2-positive breast tumors.