抗 CD44 单克隆抗体在小鼠食管癌异种移植模型中的抗肿瘤活性

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, C 44 Mab‑5 and C 44 Mab‑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 C 44 Mab‑46‑mG 2a ) to evaluate the antitumor activities against CD44‑positive cells. Both 5‑mG 2a and C 44 Mab‑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 C 44 Mab‑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 C 44 Mab‑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 C 44 Mab‑46‑mG 2a could exert antitumor activities against CD44‑positive cancers and be a promising therapeutic regimen for tumors.