Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-Antigens
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 immunothe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2292 |
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| author | Paul Schossig Ebru Coskun Ruza Arsenic David Horst Jalid Sehouli Eva Bergmann Nadine Andresen Christian Sigler Antonia Busse Ulrich Keller Sebastian Ochsenreither |
| author_facet | Paul Schossig Ebru Coskun Ruza Arsenic David Horst Jalid Sehouli Eva Bergmann Nadine Andresen Christian Sigler Antonia Busse Ulrich Keller Sebastian Ochsenreither |
| author_sort | Paul Schossig |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T09:42:10Z |
| format | Article |
| id | doaj.art-bd42bfe8242845018afbdf71cc28439e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:42:10Z |
| publishDate | 2023-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bd42bfe8242845018afbdf71cc28439e2023-11-16T16:55:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243229210.3390/ijms24032292Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-AntigensPaul Schossig0Ebru Coskun1Ruza Arsenic2David Horst3Jalid Sehouli4Eva Bergmann5Nadine Andresen6Christian Sigler7Antonia Busse8Ulrich Keller9Sebastian Ochsenreither10Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Pathology, Universitätsklinikum Heidelberg, Heidelberg University, 69120 Heidelberg, GermanyInsitute of Pathology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Gynecology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyCharité Comprehensive Cancer Center, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyAdoptive 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.https://www.mdpi.com/1422-0067/24/3/2292immunotherapytumor associated antigenovarian cancercytotoxic T lymphocytesKIF20ACT45 |
| spellingShingle | Paul Schossig Ebru Coskun Ruza Arsenic David Horst Jalid Sehouli Eva Bergmann Nadine Andresen Christian Sigler Antonia Busse Ulrich Keller Sebastian Ochsenreither Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-Antigens International Journal of Molecular Sciences immunotherapy tumor associated antigen ovarian cancer cytotoxic T lymphocytes KIF20A CT45 |
| title | Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-Antigens |
| title_full | Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-Antigens |
| title_fullStr | Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-Antigens |
| title_full_unstemmed | Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-Antigens |
| title_short | Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-Antigens |
| title_sort | target selection for t cell therapy in epithelial ovarian cancer systematic prioritization of self antigens |
| topic | immunotherapy tumor associated antigen ovarian cancer cytotoxic T lymphocytes KIF20A CT45 |
| url | https://www.mdpi.com/1422-0067/24/3/2292 |
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