Anti-CD44 Variant 10 Monoclonal Antibody Exerts Antitumor Activity in Mouse Xenograft Models of Oral Squamous Cell Carcinomas.

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, C 44 Mab-18 (IgM, kappa), to recognize the variant exon 10-encoded region. In the present study, a mouse IgG 2a version of C 44 Mab-18 (C 44 Mab-18-mG 2a ) was generated to evaluate the antitumor activities against CD44-positive cells compared with the previously established anti-pan CD44 mAb, C 44 Mab-46-mG 2a . C 44 Mab-18-mG 2a exhibited higher reactivity compared with C 44 Mab-46-mG 2a to CD44v3-10-overexpressed CHO-K1 (CHO/CD44v3-10) and oral squamous cell carcinoma cell lines (HSC-2 and SAS) in flow cytometry. C 44 Mab-18-mG 2a exerted a superior antibody-dependent cellular cytotoxicity (ADCC) against CHO/CD44v3-10. In contrast, C 44 Mab-46-mG 2a showed a superior complement-dependent cytotoxicity (CDC) against CHO/CD44v3-10. A similar tendency was observed in ADCC and CDC against HSC-2 and SAS. Furthermore, administering C 44 Mab-18-mG 2a or C 44 Mab-46-mG 2a significantly suppressed CHO/CD44v3-10, HSC-2, and SAS xenograft tumor growth compared with the control mouse IgG 2a . These results indicate that C 44 Mab-18-mG 2a could be a promising therapeutic regimen for CD44v10-positive tumors.