Defucosylated Anti-CD44 Monoclonal Antibodies Exert Antitumor Activities against Esophageal Tumor Xenograft

Abstract

CD44 is a type I transmembrane glycoprotein, which is associated with poor prognosis in various solid tumors. Since CD44 plays critical roles 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. We previously developed anti‐pan-CD44 mAbs, C44Mab-5 and C44Mab-46, which can recognize both CD44 standard (CD44s) and variant isoforms. In the present study, a defucosylated mouse IgG2a version of the anti-pan-CD44 mAbs (5-mG2a-f and C44Mab-46-mG2a-f) was generated to evaluate the antitumor activities against CD44-positive cells. Both 5-mG2a-f and C44Mab-46-mG2a-f recognized CD44s-overexpressed CHO-K1 (CHO/CD44s) cells and esophageal tumor cell line (KYSE770) in flow cytometry. Furthermore, both 5-mG2a-f and C44Mab-46-mG2a-f could activate effector cells in the presence of CHO/CD44s cells and exhibited the complement‐dependent cytotoxicity against both CHO/CD44s and KYSE770 cells. Furthermore, the administration of 5-mG2a-f and C44Mab-46-mG2a-f significantly suppressed CHO/CD44s and KYSE770 xenograft tumor development compared with the control defucosylated mouse IgG2a. These results indicate that 5-mG2a-f and C44Mab-46-mG2a-f could exert antitumor activities against CD44-positive cancers and could be a promising therapeutic regimen for tumors.