ArticleInternational journal of molecular sciences2024
Trastuzumab-Mediated Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Enhances Natural Killer Cell Cytotoxicity in HER2-Overexpressing Ovarian Cancer.
Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Bispecific antibody AP402 targets p95HER2 and induces costimulation through CD137 to improve efficacy for HER2-positive tumors.Molecular medicine (Cambridge, Mass.) · 2026Article
- Engineering Bi-Specific CAR-NK Cells to Restore Antibody-Dependent Cellular Cytotoxicity in Solid Tumors.Cells · 2026Article
- Natural Killer Cell Therapy in Ovarian Cancer: From Preclinical Potentials to Clinical Applications and Combination Strategies.International journal of biological sciences · 2026Review
- Bioinformatics and artificial intelligence in genomic data analysis: current advances and future directions.Molecular genetics and genomics : MGG · 2025Review
- Review
- Nuclear receptor subfamily 1 group D member 2 induces chemoresistance in ovarian cancer by regulating ferroptosis and immune infiltration.Discover oncology · 2025Article
- Significance of Notch Signaling in Salivary Gland Development and Diseases.Journal of clinical medicine · 2025Review
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Authors and funding
9 authors.
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Abstract
Ovarian cancer is the deadliest gynecologic cancer. Although human epidermal growth factor receptor-2 (HER2) overexpression, a poor prognostic molecular marker in ovarian cancer, is found in almost 30% of ovarian cancer cases, there are no established therapies for HER2-overexpressing ovarian cancer. In this study, we investigated the efficacy of combined samfenet, a biosimilar compound of trastuzumab, and natural killer (NK) cells in preclinical model of HER2-overexpressing ovarian cancer. Firstly, we screened the HER2 expression in three ovarian cancer cell lines and eight ovarian cancer patient-derived tumor xenograft (PDTX) samples. Then, immunohistochemistry and silver in situ hybridization (SISH) were performed following clinical criteria. HER2-overexpressing cells exhibited the highest sensitivity to samfenet compared with low-HER2-expressing cells. In addition, the combination of samfenet with natural killer (NK) cells resulted in significantly enhanced sensitivity to HER2-overexpressing cells and showed a significant antitumor effect on PDTX mice compared with monotherapy. It is known that anti-HER2-humanized IgG1 monoclonal antibodies, including trastuzumab, induce antibody-dependent cellular cytotoxicity (ADCC). Consequently, the combination of samfenet with NK cells demonstrated NK cell-mediated ADCC, as confirmed using an in vitro NK cytotoxicity assay and in vivo antitumor efficacy. A transferase dUTP nick end labeling (TUNEL) assay using xenografted tumors further supported the ADCC effects based on the increase in the number of apoptotic cells in the combination group. Furthermore, high HER2 expression was associated with shorter progression-free survival and overall survival based on public mRNA expression data. In this study, we demonstrated that the combination of samfenet and NK cell therapy could be a promising treatment strategy for patients with HER2-overexpressing ovarian cancer, through ADCC effects. Therefore, this study supports a rationale for further clinical studies of the combination of samfenet and NK cells as a therapy for patients with HER2-overexpressing ovarian cancer.
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