Antitumor Activity by an Anti-CD44 Variant 9 Monoclonal Antibody in Gastric and Colorectal Cancer Xenograft Models

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, C₄₄Mab-1 (mouse, IgG₁, kappa), was previously established. C₄₄Mab-1 recognizes the variant exon 9-encoded region and applies to multiple research techniques. A mouse IgG_2a version of C₄₄Mab-1 (C₄₄Mab-1-mG_2a) was generated to evaluate the in vitro and in vivo antitumor activities using gastric and colorectal cancer cell lines. C₄₄Mab-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. C₄₄Mab-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 C₄₄Mab-1-mG_2a significantly suppressed CHO/CD44v3-10, MKN45, and COLO205 xenograft tumor growth compared with control mouse IgG_2a. These results indicated that C₄₄Mab-1-mG_2a, which possesses ADCC/CDC activities, could be applied to the mAb-based therapy against CD44v9-positive carcinomas.