Preprint Article Version 4 Preserved in Portico This version is not peer-reviewed

Establishment of a Novel Cancer-Specific Anti-HER2 Monoclonal Antibody H2Mab-250/H2CasMab-2 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)
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)

A peer-reviewed article of this Preprint also exists.

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. 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 can be beneficial in reducing the adverse effects. In this study, we established a novel cancer-specific anti-HER2 antibody, named H2Mab-250/H2CasMab-2 (IgG1, kappa). H2Mab-250 reacted with HER2-positive breast cancer BT-474 and SK-BR-3 cells. Importantly, H2Mab-250 did not react with 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. Furthermore, a core-fucose deleted IgG2a-type H2Mab-250 (H2Mab-250-mG2a-f) could trigger the antibody-dependent cellular cytotoxicity activity to BT-474, but not to HaCaT cells. Furthermore, H2Mab-250-mG2a-f exhibited an in vivo antitumor effect against BT-474 xenograft. Immunohistochemical analysis demonstrated that H2Mab-250 possesses much higher reactivity to the HER2-positive breast cancer tissues compared to H2Mab-119, and did not react with normal tissues, including heart, breast, stomach, lung, colon, kidney, and esophagus. The epitope mapping demonstrated that the Trp614 of HER2 domain IV mainly contributes to the recognition by H2Mab-250. H2Mab-250 could contribute to the development of chimeric antigen receptor-T or antibody-drug conjugates without adverse effects for breast cancer therapy.

Keywords

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

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Comments (1)

Comment 1
Received: 28 December 2023
Commenter: Hiroyuki Suzuki
Commenter's Conflict of Interests: Author
Comment: For revision, we newly added Fig. 3, Fig. 5,  Fig. 6A, B, and discussion.
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