Ishikawa, K.; Suzuki, H.; Ohishi, T.; Li, G.; Tanaka, T.; Kawada, M.; Ohkoshi, A.; Kaneko, M. K.; Katori, Y.; Kato, Y. Anti-CD44 Variant 10 Monoclonal Antibody Exerts Antitumor Activity in Mouse Xenograft Models of Oral Squamous Cell Carcinomas. Preprints2024, 2024080238. https://doi.org/10.20944/preprints202408.0238.v1
APA Style
Ishikawa, K., Suzuki, H., Ohishi, T., Li, G., Tanaka, T., Kawada, M., Ohkoshi, A., Kaneko, M. K., Katori, Y., & Kato, Y. (2024). Anti-CD44 Variant 10 Monoclonal Antibody Exerts Antitumor Activity in Mouse Xenograft Models of Oral Squamous Cell Carcinomas. Preprints. https://doi.org/10.20944/preprints202408.0238.v1
Chicago/Turabian Style
Ishikawa, K., Yukio Katori and Yukinari Kato. 2024 "Anti-CD44 Variant 10 Monoclonal Antibody Exerts Antitumor Activity in Mouse Xenograft Models of Oral Squamous Cell Carcinomas" Preprints. https://doi.org/10.20944/preprints202408.0238.v1
Abstract
CD44 regulates cell adhesion, proliferation, survival, and stemness and has been considered a tumor therapy target. CD44 possesses the shortest CD44 standard (CD44s) and a variety of CD44 variant (CD44v) isoforms. Since the expression of CD44v is restricted in epithelial cells and carcinomas compared to CD44s, CD44v has been considered a promising target for monoclonal antibody (mAb) therapy. We previously developed an anti‐CD44v10 mAb, C44Mab-18 (IgM, kappa) to recognize the variant exon 10-encoded region. In the present study, a mouse IgG2a version of C44Mab-18 (C44Mab-18-mG2a) was generated to evaluate the antitumor activities against CD44-positive cells compared with previously established anti-pan CD44 mAb, C44Mab-46-mG2a. C44Mab-18-mG2a exhibited higher reactivity compared with C44Mab-46-mG2a to CD44v3–10-overexpressed CHO-K1 (CHO/CD44v3–10) and oral squamous cell carcinoma cell lines (HSC-2 and SAS) in flow cytometry. C44Mab-18-mG2a exerted a superior antibody‐dependent cellular cytotoxicity (ADCC) against CD44v3–10. In contrast, C44Mab-46-mG2a showed a superior complement‐dependent cytotoxicity (CDC) against CD44v3–10. A similar tendency was observed in ADCC and CDC against HSC-2 and SAS. Furthermore, administering C44Mab-18-mG2a or C44Mab-46-mG2a significantly suppressed CD44v3–10, HSC-2, and SAS xenograft tumor growth compared with the control mouse IgG2a. These results indicate that C44Mab-18-mG2a could be a promising therapeutic regimen for CD44v10-positive tumors.
Medicine and Pharmacology, Oncology and Oncogenics
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