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

Background: 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 CD44v variant exon 9-encoded region and applies to multiple research techniques. Methods: A mouse IgG2a version of C44Mab-1 (C44Mab-1-mG2a) was generated to evaluate the in vitro and in vivo antitumor activities using gastric and colorectal cancer cell lines. Results: C44Mab-1-mG2a 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-mG2a exhibited both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against CHO/CD44v3–10, MKN45, and COLO205. Furthermore, administration of C44Mab-1-mG2a significantly suppressed CHO/CD44v3–10, MKN45, and COLO205 xenograft tumor growth compared with control mouse IgG2a. Conclusions: These results indicated that C44Mab-1-mG2a, which possesses ADCC/CDC activities, could be applied to the mAb-based therapy against CD44v9-positive carcinomas.