Version 1
: Received: 13 September 2023 / Approved: 13 September 2023 / Online: 14 September 2023 (05:00:22 CEST)
Version 2
: Received: 24 October 2023 / Approved: 24 October 2023 / Online: 24 October 2023 (08:08:28 CEST)
Version 3
: Received: 24 November 2023 / Approved: 27 November 2023 / Online: 28 November 2023 (03:35:30 CET)
Version 4
: Received: 26 December 2023 / Approved: 26 December 2023 / Online: 28 December 2023 (02:42:29 CET)
Version 5
: Received: 4 January 2024 / Approved: 4 January 2024 / Online: 4 January 2024 (11:30:55 CET)
How to cite:
Suzuki, H.; Kaneko, M.K.; Kato, Y. A Cancer-Specific Monoclonal Antibody against HER2 for Breast Cancers. Preprints2023, 2023090906. https://doi.org/10.20944/preprints202309.0906.v1
Suzuki, H.; Kaneko, M.K.; Kato, Y. A Cancer-Specific Monoclonal Antibody against HER2 for Breast Cancers. Preprints 2023, 2023090906. https://doi.org/10.20944/preprints202309.0906.v1
Suzuki, H.; Kaneko, M.K.; Kato, Y. A Cancer-Specific Monoclonal Antibody against HER2 for Breast Cancers. Preprints2023, 2023090906. https://doi.org/10.20944/preprints202309.0906.v1
APA Style
Suzuki, H., Kaneko, M.K., & Kato, Y. (2023). A Cancer-Specific Monoclonal Antibody against HER2 for Breast Cancers. Preprints. https://doi.org/10.20944/preprints202309.0906.v1
Chicago/Turabian Style
Suzuki, H., Mika K Kaneko and Yukinari Kato. 2023 "A Cancer-Specific Monoclonal Antibody against HER2 for Breast Cancers" Preprints. https://doi.org/10.20944/preprints202309.0906.v1
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
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.