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

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, 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.

SUBMITTER: Tawara M 

PROVIDER: S-EPMC12470293 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature