Suzuki, H.; Ohishi, T.; Tanaka, T.; Kaneko, M. K.; Kato, Y. Anti-HER2 cancer-specific mAb, H2Mab-250-hG1 possesses higher complement-dependent cytotoxicity than trastuzumab. Preprints2024, 2024070864. https://doi.org/10.20944/preprints202407.0864.v1
APA Style
Suzuki, H., Ohishi, T., Tanaka, T., Kaneko, M. K., & Kato, Y. (2024). Anti-HER2 cancer-specific mAb, H2Mab-250-hG<sub>1</sub> possesses higher complement-dependent cytotoxicity than trastuzumab. Preprints. https://doi.org/10.20944/preprints202407.0864.v1
Chicago/Turabian Style
Suzuki, H., Mika K. Kaneko and Yukinari Kato. 2024 "Anti-HER2 cancer-specific mAb, H2Mab-250-hG<sub>1</sub> possesses higher complement-dependent cytotoxicity than trastuzumab" Preprints. https://doi.org/10.20944/preprints202407.0864.v1
Abstract
Cancer-specific monoclonal antibodies (CasMabs) that recognize cancer-specific antigens with in vivo antitumor efficacy are innovative therapeutic strategies for minimizing the adverse effects. We previously established a cancer-specific anti-human epidermal growth factor receptor 2 (HER2)monoclonal antibody (mAb), H2Mab-250/H2CasMab-2. In flow cytometry and immunohistochemistry, H2Mab-250 reacted with HER2-positive breast cancer cells but did not show the reactivity to normal epithelial cells. In contrast, a clinically approved anti-HER2 mAb, trastuzumab, strongly recognizes both breast cancer and normal epithelial cells in flow cytometry. The human IgG1version of H2Mab-250 (H2Mab-250-hG1) possesses compatible in vivoantitumor effects against breast cancer xenografts with trastuzumab despite the lower affinity and effector activation than trastuzumab in vitro. This study compared the antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cellular cytotoxicity (CDC) between H2Mab-250-hG1 and trastuzumab. Both H2Mab-250-hG1 and trastuzumab showed ADCC activity against CHO/HER2 and breast cancer cell lines (BT-474 and SK-BR-3) in the presence of human natural killer cells. Some tendency was observed that trastuzumab showed a more significant ADCC effect compared to H2Mab-250-hG1.Importantly, H2Mab-250-hG1exhibited superior CDC activity in these cells compared to trastuzumab. Similar results were obtained in mouse IgG2a types of both H2Mab-250 and trastuzumab. These results suggest the different contributions of ADCC and CDC activities tothe antitumor effects of H2Mab-250-hG1 and trastuzumab and indicate the future direction for the clinical development of H2Mab-250-hG1 against HER2-positive tumors.
Medicine and Pharmacology, Oncology and Oncogenics
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