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, 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.