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CD70 antibody‐drug conjugate: A potential novel therapeutic agent for ovarian cancer
- 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.
- Subjects :
- Cancer Research
Antibody-drug conjugate
Immunoconjugates
endocrine system diseases
medicine.medical_treatment
NF‐κB‐p65
xenograft model
Antineoplastic Agents
Transfection
Mice
In vivo
Cell Line, Tumor
Animals
Humans
Cytotoxic T cell
Medicine
Gene Silencing
Aged
Cell Proliferation
Ovarian Neoplasms
Cisplatin
Chemotherapy
Cluster of differentiation
business.industry
Transcription Factor RelA
Original Articles
General Medicine
Middle Aged
medicine.disease
Xenograft Model Antitumor Assays
female genital diseases and pregnancy complications
Tumor Burden
Drug Discovery and Delivery
CD70
ovarian cancer
Oncology
Drug Resistance, Neoplasm
Cell culture
Cancer research
Original Article
Female
business
Ovarian cancer
neoadjuvant chemotherapy
CD27 Ligand
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 13497006 and 13479032
- Volume :
- 112
- Database :
- OpenAIRE
- Journal :
- Cancer Science
- Accession number :
- edsair.doi.dedup.....49294eb7a267a6259ea093926e4918b4