Abstract
CD44 variants (CD44v) play essential roles in the promotion of tumor metastasis, maintenance of cancer stem cell properties, and resistance to treatments. Therefore, the development of anti-CD44v mAbs is essential for targeting CD44v-positive tumor cells. An anti-CD44v9 mAb, C(44)Mab-1 (mouse, IgG(1), kappa), was previously established. C(44)Mab-1 recognizes the variant exon 9-encoded region and applies to multiple research techniques. A mouse IgG(2a) version of C(44)Mab-1 (C(44)Mab-1-mG(2a)) was generated to evaluate the in vitro and in vivo antitumor activities using gastric and colorectal cancer cell lines. C(44)Mab-1-mG(2a) showed a reactivity to CD44v3-10-overexpressed Chinese hamster ovary-K1 (CHO/CD44v3-10), gastric cancer MKN45, and colorectal cancer COLO205 in flow cytometry. C(44)Mab-1-mG(2a) exhibited both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against CHO/CD44v3-10, MKN45, and COLO205. Furthermore, administration of C(44)Mab-1-mG(2a) significantly suppressed CHO/CD44v3-10, MKN45, and COLO205 xenograft tumor growth compared with control mouse IgG(2a). These results indicated that C(44)Mab-1-mG(2a), which possesses ADCC/CDC activities, could be applied to the mAb-based therapy against CD44v9-positive carcinomas.