Kurzfassung

Part of a multi-center translational oncology program to explore mutant immunogenic epitopes for T cell therapy of malignant melanoma, our subproject aims to define tumor-specific antigens (TSAs) by exome and transcriptome sequencing for adoptive T cell therapy (ATT) with TSA-specific T cell receptor (TCR)-transgenic T cells. Melanoma from HLA-A*02:01(A2.1) patient will be analyzed for somatic mutations and their potency to encode TSA peptides presented by A2.1. Candidate peptides will be...Part of a multi-center translational oncology program to explore mutant immunogenic epitopes for T cell therapy of malignant melanoma, our subproject aims to define tumor-specific antigens (TSAs) by exome and transcriptome sequencing for adoptive T cell therapy (ATT) with TSA-specific T cell receptor (TCR)-transgenic T cells. Melanoma from HLA-A*02:01(A2.1) patient will be analyzed for somatic mutations and their potency to encode TSA peptides presented by A2.1. Candidate peptides will be screened for their recognition by autologous T cells. A2.1-transgenic mice will be immunized with selected peptides to generate TSA-reactive CD8+ T cells. TSA-specific TCRs will be cloned and their functional activity will be analyzed in vitro and in vivo in tumor-transplanted xenograft models. We will also determine the presence of TSA-specific T cells in peripheral blood and tumor samples sequentially collected from candidate patients and the heterogeneity of TSA expression in distinct tumor lesions. Overall, our project will demonstrate how exome and transcriptome data can be exploited to define TSAs and to generate TSA-specific TCR T cells for personalized ATT of cancer patients.

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