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:
Kaneko, M.K.; Suzuki, H.; Kato, Y. Establishment of a Novel Cancer-Specific Anti-HER2 Monoclonal Antibody H2Mab-250/H2CasMab-2 for Breast Cancers. Preprints2023, 2023090906. https://doi.org/10.20944/preprints202309.0906.v5
Kaneko, M.K.; Suzuki, H.; Kato, Y. Establishment of a Novel Cancer-Specific Anti-HER2 Monoclonal Antibody H2Mab-250/H2CasMab-2 for Breast Cancers. Preprints 2023, 2023090906. https://doi.org/10.20944/preprints202309.0906.v5
Kaneko, M.K.; Suzuki, H.; Kato, Y. Establishment of a Novel Cancer-Specific Anti-HER2 Monoclonal Antibody H2Mab-250/H2CasMab-2 for Breast Cancers. Preprints2023, 2023090906. https://doi.org/10.20944/preprints202309.0906.v5
APA Style
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. Preprints. https://doi.org/10.20944/preprints202309.0906.v5
Chicago/Turabian Style
Kaneko, M.K., Hiroyuki Suzuki and Yukinari Kato. 2024 "Establishment of a Novel Cancer-Specific Anti-HER2 Monoclonal Antibody H2Mab-250/H2CasMab-2 for Breast Cancers" Preprints. https://doi.org/10.20944/preprints202309.0906.v5
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-250did notreact 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 demonstratedthat 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.
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
Commenter:
The commenter has declared there is no conflict of interests.
https://fatetherapeutics.com/pipeline/immuno-oncology-candidates/ft825/
2023 SITC Poster Presentation: "Development of FT825/ONO-8250: an off-the-shelf CAR-T cell with preferential HER2 targeting and engineered to enable multi-antigen targeting, improve trafficking, and overcome immunosuppression."
https://fatetherapeutics.com/wp-content/uploads/2023/11/SITC-2023-FT825-ONO8250-Poster-Final.pdf