Antitumor activities of anti‑CD44 monoclonal antibodies in mouse xenograft models of esophageal cancer.

Abstract

CD44 is a type I transmembrane glycoprotein associated with poor prognosis in various solid tumors. Since CD44 plays a critical role in tumor development by regulating cell adhesion, survival, proliferation and stemness, it has been considered a target for tumor therapy. Anti‑CD44 monoclonal antibodies (mAbs) have been developed and applied to antibody‑drug conjugates and chimeric antigen receptor‑T cell therapy. Anti-pan‑CD44 mAbs, C₄₄Mab‑5 and C₄₄Mab‑46, which recognize both CD44 standard (CD44s) and variant isoforms were previously developed. The present study generated a mouse IgG_2a version of the anti‑pan‑CD44 mAbs (5‑mG_2a and C₄₄Mab‑46‑mG_2a) to evaluate the antitumor activities against CD44‑positive cells. Both 5‑mG_2a and C₄₄Mab‑46‑mG_2a recognized CD44s‑overexpressed CHO‑K1 (CHO/CD44s) cells and esophageal tumor cell line (KYSE770) in flow cytometry. Furthermore, both 5‑mG_2a and C₄₄Mab‑46‑mG_2a could activate effector cells in the presence of CHO/CD44s cells and exhibited complement-dependent cytotoxicity against both CHO/CD44s and KYSE770 cells. Furthermore, the administration of 5‑mG_2a and C₄₄Mab‑46‑mG_2a significantly suppressed CHO/CD44s and KYSE770 xenograft tumor development compared with the control mouse IgG_2a. These results indicate that 5‑mG_2a and C₄₄Mab‑46‑mG_2a could exert antitumor activities against CD44‑positive cancers and be a promising therapeutic regimen for tumors.