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Kaneko, M. K., Suzuki, H., & Kato, Y. (2024). Establishment of a Novel Cancer-specific Anti-HER2 Monoclonal Antibody H2Mab-250/H2CasMab-2 for breast cancers. Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 43(2), 35-43.
Kaneko, M. K., Suzuki, H., & Kato, Y. (2024). Establishment of a Novel Cancer-specific Anti-HER2 Monoclonal Antibody H2Mab-250/H2CasMab-2 for breast cancers. Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 43(2), 35-43.
Kaneko, M. K., Suzuki, H., & Kato, Y. (2024). Establishment of a Novel Cancer-specific Anti-HER2 Monoclonal Antibody H2Mab-250/H2CasMab-2 for breast cancers. Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 43(2), 35-43.
Kaneko, M. K., Suzuki, H., & Kato, Y. (2024). Establishment of a Novel Cancer-specific Anti-HER2 Monoclonal Antibody H2Mab-250/H2CasMab-2 for breast cancers. Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, 43(2), 35-43.
Abstract
Overexpression of human epidermal growth factor receptor 2 (HER2) in breast and gastric cancers is an important target for monoclonal antibody (mAb) therapy such as trastuzumab. All therapeutic mAbs, including anti-HER2 mAbs, exhibit adverse effects probably due to the recognition of antigens expressed in normal cells. Therefore, tumor-selective or specific mAbs have been desired to reduce adverse effects. In this study, we provide a strategy for the selection of cancer-specific mAb against HER2. We screened more than 200 of anti-HER2 mAbs obtained by our laboratory and established a novel cancer-specific anti-HER2 antibody, H2Mab-250 (IgG1, kappa). H2Mab-250 reacted with HER2-positive breast cancer BT-474 and SK-BR-3 cells. Importantly, H2Mab-250 never showed reactivity to non-transformed normal epithelial cells (HaCaT and MCF 10A) and immortalized normal epithelial cells in flow cytometry. In contrast, most anti-HER2 mAbs including H2Mab-119 (IgG1, kappa) reacted with both cancer and normal epithelial cells. The epitope mapping revealed that H2Mab-250 recognized the domain VI of HER2 and the Trp614 mainly contributes to the recognition by H2Mab-250. In immunohistochemical analysis, H2Mab-250 exhibited a superior reactivity to HER2-positive breast cancer section compared to H2Mab-119. Importantly, H2Mab-250 never showed any reactivity to normal tissues by immunohistochemical analysis. The strategy to select cancer-specific mAbs would contribute to the development of novel antibodies and modalities for cancer therapy.
Medicine and Pharmacology, Oncology and Oncogenics
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