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

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‐...

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Bibliographic Details
Published in:Cancer science 2021-09, Vol.112 (9), p.3655-3668
Main Authors: Shiomi, Mayu, Matsuzaki, Shinya, Serada, Satoshi, Matsuo, Koji, Mizuta‐Odani, Chihiro, Jitsumori, Mariko, Nakae, Ruriko, Matsuzaki, Satoko, Nakagawa, Satoshi, Hiramatsu, Kosuke, Miyoshi, Ai, Kobayashi, Eiji, Kimura, Toshihiro, Ueda, Yutaka, Yoshino, Kiyoshi, Naka, Tetsuji, Kimura, Tadashi
Format: Article
Language:English
Subjects:
Antibodies
B cells
Biopharmaceutics
Cancer
Cancer therapies
CD70
CD70 antigen
Chemotherapy
Cisplatin
Clinical trials
Cloning
Cytotoxicity
Drug therapy
Ethylenediaminetetraacetic acid
Health aspects
Laboratories
Lymphoma
Monoclonal antibodies
neoadjuvant chemotherapy
NF‐κB‐p65
Original
Ovarian cancer
Penicillin
Proteins
siRNA
Tumor cell lines
Viral antibodies
Western blotting
Womens health
xenograft model
Xenografts
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Summary: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 
ISSN:1347-9032
1349-7006
DOI:10.1111/cas.15027