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CD70 antibody‐drug conjugate: A potential novel therapeutic agent for ovarian cancer

Authors :
Satoko Matsuzaki
Ruriko Nakae
Yutaka Ueda
Kiyoshi Yoshino
Eiji Kobayashi
Satoshi Nakagawa
Chihiro Mizuta-Odani
Mayu Shiomi
Ai Miyoshi
Toshihiro Kimura
Shinya Matsuzaki
Satoshi Serada
Mariko Jitsumori
Koji Matsuo
Kosuke Hiramatsu
Tetsuji Naka
Tadashi Kimura
Source :
Cancer Science
Publication Year :
2021
Publisher :
Wiley, 2021.

Abstract

This study aimed to investigate the cytotoxicity of a cluster of differentiation 70 antibody‐drug conjugate (CD70‐ADC) against ovarian cancer in in vitro and in vivo xenograft models. CD70 expression was assessed in clinical samples by immunohistochemical analysis. Western blotting and fluorescence‐activated cell sorting analyses were used to determine CD70 expression in the ovarian cancer cell lines A2780 and SKOV3, and in the cisplatin‐resistant ovarian cancer cell lines A2780cisR and SKOV3cisR. CD70 expression after cisplatin exposure was determined in A2780 cells transfected with mock‐ or nuclear factor (NF)‐κB‐p65‐small interfering RNA. We developed an ADC with an anti‐CD70 monoclonal antibody linked to monomethyl auristatin F and investigated its cytotoxic effect. We examined 63 ovarian cancer clinical samples; 43 (68.3%) of them expressed CD70. Among patients with advanced stage disease (n = 50), those who received neoadjuvant chemotherapy were more likely to exhibit high CD70 expression compared to those who did not (55.6% [15/27] vs 17.4% [4/23], P<br />The immunohistochemical analysis of ovarian cancer specimens revealed that cluster of differentiation 70 (CD70) is expressed in approximately 70% of patients who received platinum‐based neoadjuvant chemotherapy. CD70 is induced in cisplatin‐treated ovarian cancer cells and is strongly expressed in platinum‐resistant cells. The CD70 antibody‐drug conjugate is effective against CD70‐expressing ovarian cancer both in vitro and in vivo. Our translational research indicates that the effectiveness of CD70 antibody‐drug conjugate merits further investigation as a novel therapeutic strategy for women with ovarian cancer.

Details

ISSN :
13497006 and 13479032
Volume :
112
Database :
OpenAIRE
Journal :
Cancer Science
Accession number :
edsair.doi.dedup.....49294eb7a267a6259ea093926e4918b4