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.v2
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.v2
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.v2
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.v2
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.v2
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.
Commenter: Hiroyuki Suzuki
Commenter's Conflict of Interests: Author
630–622 (ver. 1) to 603–622 (Line 256)
I608A to L608A (Figure 4C, E)
We added the introduction (Line 51-57).