Antitumor activities of anti‑CD44 monoclonal antibodies in mouse xenograft models of esophageal cancer
Kenichiro Ishikawa, Hiroyuki Suzuki, Tomokazu Ohishi, Takuro Nakamura, Miyuki Yanaka, Guanjie Li, Tomohiro Tanaka, Akira Ohkoshi, Manabu Kawada, Mika K. Kaneko, Yukio Katori, Yukinari Kato
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, C<sub>44</sub>Mab‑5 and C<sub>44</sub>Mab‑46, which recognize both CD44 standard (CD44s) and variant isoforms were previously developed. The present study generated a mouse IgG<sub>2a</sub> version of the anti‑pan‑CD44 mAbs (5‑mG<sub>2a</sub> and C<sub>44</sub>Mab‑46‑mG<sub>2a</sub>) to evaluate the antitumor activities against CD44‑positive cells. Both 5‑mG<sub>2a</sub> and C<sub>44</sub>Mab‑46‑mG<sub>2a</sub> recognized CD44s‑overexpressed CHO‑K1 (CHO/CD44s) cells and esophageal tumor cell line (KYSE770) in flow cytometry. Furthermore, both 5‑mG<sub>2a</sub> and C<sub>44</sub>Mab‑46‑mG<sub>2a</sub> 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<sub>2a</sub> and C<sub>44</sub>Mab‑46‑mG<sub>2a</sub> significantly suppressed CHO/CD44s and KYSE770 xenograft tumor development compared with the control mouse IgG<sub>2a</sub>. These results indicate that 5‑mG<sub>2a</sub> and C<sub>44</sub>Mab‑46‑mG<sub>2a</sub> could exert antitumor activities against CD44‑positive cancers and be a promising therapeutic regimen for tumors.