Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

A Cancer-Specific Monoclonal Antibody against HER2 for Breast Cancers

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)

How to cite: Suzuki, H.; Kaneko, M.K.; Kato, Y. A Cancer-Specific Monoclonal Antibody against HER2 for Breast Cancers. Preprints 2023, 2023090906. Suzuki, H.; Kaneko, M.K.; Kato, Y. A Cancer-Specific Monoclonal Antibody against HER2 for Breast Cancers. Preprints 2023, 2023090906.


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.


HER2; cancer-specific monoclonal antibody; screening; epitope; flow cytometry


Medicine and Pharmacology, Oncology and Oncogenics

Comments (1)

Comment 1
Received: 24 October 2023
Commenter: Hiroyuki Suzuki
Commenter's Conflict of Interests: Author
Comment: We corrected some errors in text and Figure.

630–622 (ver. 1) to 603–622 (Line 256)
I608A to L608A (Figure 4C, E)

We added the introduction (Line 51-57).
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