Abstract
CD44 variant (CD44v) isoforms are involved in promoting cancer metastasis, sustaining cancer stem cell (CSC) properties, and conferring resistance to therapeutic interventions. Consequently, the development of monoclonal antibodies (mAbs) targeting CD44v represents a crucial strategy for eliminating CD44v-positive cancer cells. Previously, an anti-CD44v6 mAb, C(44)Mab-9 (mouse IgG(1), κ), was established. C(44)Mab-9 recognizes explicitly the epitope encoded by the variant exon 6-encoded region of CD44 and applies to flow cytometry, western blotting, and immunohistochemistry. To assess the therapeutic potential, a mouse IgG(2a) isotype of C(44)Mab-9 (designated C(44)Mab-9-mG(2a)) was generated, and the in vitro and in vivo antitumor activities were evaluated using gastric and colorectal cancer cell lines. C(44)Mab-9-mG(2a) demonstrated specific binding to CD44v3-10-overexpressed Chinese hamster ovary cells (CHO/CD44v3-10), as well as gastric cancer (NUGC-4) and colorectal cancer (COLO201 and COLO205) in flow cytometry. C(44)Mab-9-mG(2a) exerted antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against CHO/CD44v3-10, NUGC-4, COLO201, and COLO205. Moreover, systemic administration of C(44)Mab-9-mG(2a) significantly inhibited tumor growth in CHO/CD44v3-10, NUGC-4, COLO201, and COLO205 xenografts compared with the control IgG(2a). These findings indicate that C(44)Mab-9-mG(2a) could be applied to the mAb-based therapy against CD44v6-positive tumors.