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Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-Antigens
Paul Schossig1, Ebru Coskun1,2, Ruza Arsenic3
1Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
Abstract:
Adoptive T cell-receptor therapy (ACT) could represent a promising approach in the targeted treatment of epithelial ovarian cancer (EOC). However, the identification of suitable tumor-associated antigens (TAAs) as targets is challenging. We identified and prioritized TAAs for ACT and other immunotherapeutic interventions in EOC. A comprehensive list of pre-described TAAs was created and candidates were prioritized, using predefined weighted criteria. Highly ranked TAAs were immunohistochemically stained in a tissue microarray of 58 EOC samples to identify associations of TAA expression with grade, stage, response to platinum, and prognosis. Preselection based on expression data resulted in 38 TAAs, which were prioritized. Along with already published Cyclin A1, the TAAs KIF20A, CT45, and LY6K emerged as most promising targets, with high expression in EOC samples and several identified peptides in ligandome analysis. Expression of these TAAs showed prognostic relevance independent of molecular subtypes. By using a systematic vetting algorithm, we identified KIF20A, CT45, and LY6K to be promising candidates for immunotherapy in EOC. Results are supported by IHC and HLA-ligandome data. The described method might be helpful for the prioritization of TAAs in other tumor entities.
Insights
Identifying novel tumor-associated antigens (TAAs) is crucial for epithelial ovarian cancer (EOC) immunotherapy. This study highlights KIF20A, CT45, and LY6K as promising TAAs for adoptive T cell-receptor therapy (ACT) in EOC.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Adoptive T cell-receptor therapy (ACT) shows promise for epithelial ovarian cancer (EOC).
- Identifying suitable tumor-associated antigens (TAAs) for ACT in EOC is a significant challenge.
- Effective TAAs are needed to enhance targeted immunotherapeutic strategies for EOC.
Purpose of the Study:
- To identify and prioritize TAAs for ACT and other immunotherapies in epithelial ovarian cancer (EOC).
- To evaluate the expression and prognostic relevance of potential TAAs in EOC patient samples.
- To validate promising TAAs using immunohistochemistry and HLA-ligandome analysis.
Main Methods:
- Systematic review and prioritization of pre-described TAAs using weighted criteria.
- Immunohistochemical staining of TAAs in a tissue microarray of 58 EOC samples.
- Analysis of TAA expression association with clinical parameters and prognostic relevance, supported by HLA-ligandome data.
Main Results:
- 38 TAAs were preselected based on expression data and further prioritized.
- KIF20A, CT45, and LY6K emerged as highly promising TAAs, alongside Cyclin A1.
- These TAAs demonstrated significant expression in EOC and prognostic relevance, independent of molecular subtypes.
Conclusions:
- KIF20A, CT45, and LY6K are identified as promising candidates for EOC immunotherapy, particularly for ACT.
- The study validates these TAAs using immunohistochemistry and HLA-ligandome data.
- The systematic vetting algorithm can aid TAA prioritization in other cancer types.
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