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Target selection for T-cell therapy in epithelial ovarian cancer: systematic prioritization of self-antigens

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Item Type:Article
Title:Target selection for T-cell therapy in epithelial ovarian cancer: systematic prioritization of self-antigens
Creators Name:Schossig, P. and Coskun, E. and Arsenic, R. and Horst, D. and Sehouli, J. and Bergmann, E. and Andresen, N. and Sigler, C. and Busse, A. and Keller, U. and Ochsenreither, S.
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.
Keywords:Immunotherapy, Tumor Associated Antigen, Ovarian Cancer, Cytotoxic T Lymphocytes, KIF20A, CT45, LY6K, Cyclin A1
Source:International Journal of Molecular Sciences
Page Range:2292
Date:24 January 2023
Official Publication:https://doi.org/10.3390/ijms24032292
PubMed:View item in PubMed

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