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Topics {✒️}

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Schema {🗺️}

WebPage:
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         headline:Cancer testis antigen Cyclin A1 harbors several HLA-A*02:01-restricted T cell epitopes, which are presented and recognized in vivo
         description:Cyclin A1 is a promising antigen for T cell therapy being selectively expressed in high-grade ovarian cancer (OC) and acute myeloid leukemia (AML) stem cells. For adoptive T cell therapy, a single epitope has to be selected, with high affinity to MHC class I and adequate processing and presentation by malignant cells to trigger full activation of specific T cells. In silico prediction with three algorithms indicated 13 peptides of Cyclin A1 9 to 11 amino acids of length to have high affinity to HLA-A*02:01. Ten of them proved to be affine in an HLA stabilization assay using TAP-deficient T2 cells. Their immunogenicity was assessed by repetitive stimulation of CD8+ T cells from two healthy donors with single-peptide-pulsed dendritic cells or monocytes. Intracellular cytokine staining quantified the enrichment of peptide-specific functional T cells. Seven peptides were immunogenic, three of them against both donors. Specific cell lines were cloned and used in killing assays to demonstrate recognition of endogenous Cyclin A1 in the HLA-A*02:01-positive AML cell line THP-1. Immunopeptidome analysis based on direct isolation of HLA-presented peptides by mass spectrometry of primary AML and OC samples identified four naturally presented epitopes of Cyclin A1. The immunopeptidome of HeLa cells transfected with Cyclin A1 and HLA-A*02:01 revealed six Cyclin A1-derived HLA ligands. Epitope p410–420 showed high affinity to HLA-A*02:01 and immunogenicity in both donors. It proved to be naturally presented on primary AML blast and provoked spontaneous functional response of T cells from treatment naïve OC and, therefore, warrants further development for clinical application.
         datePublished:2020-03-10T00:00:00Z
         dateModified:2021-06-25T00:00:00Z
         pageStart:1217
         pageEnd:1227
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            Epitope
            CD8 T cell
            HLA immunopeptidome
            Acute myeloid leukemia
            Ovarian carcinoma
            Oncology
            Immunology
            Cancer Research
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      headline:Cancer testis antigen Cyclin A1 harbors several HLA-A*02:01-restricted T cell epitopes, which are presented and recognized in vivo
      description:Cyclin A1 is a promising antigen for T cell therapy being selectively expressed in high-grade ovarian cancer (OC) and acute myeloid leukemia (AML) stem cells. For adoptive T cell therapy, a single epitope has to be selected, with high affinity to MHC class I and adequate processing and presentation by malignant cells to trigger full activation of specific T cells. In silico prediction with three algorithms indicated 13 peptides of Cyclin A1 9 to 11 amino acids of length to have high affinity to HLA-A*02:01. Ten of them proved to be affine in an HLA stabilization assay using TAP-deficient T2 cells. Their immunogenicity was assessed by repetitive stimulation of CD8+ T cells from two healthy donors with single-peptide-pulsed dendritic cells or monocytes. Intracellular cytokine staining quantified the enrichment of peptide-specific functional T cells. Seven peptides were immunogenic, three of them against both donors. Specific cell lines were cloned and used in killing assays to demonstrate recognition of endogenous Cyclin A1 in the HLA-A*02:01-positive AML cell line THP-1. Immunopeptidome analysis based on direct isolation of HLA-presented peptides by mass spectrometry of primary AML and OC samples identified four naturally presented epitopes of Cyclin A1. The immunopeptidome of HeLa cells transfected with Cyclin A1 and HLA-A*02:01 revealed six Cyclin A1-derived HLA ligands. Epitope p410–420 showed high affinity to HLA-A*02:01 and immunogenicity in both donors. It proved to be naturally presented on primary AML blast and provoked spontaneous functional response of T cells from treatment naïve OC and, therefore, warrants further development for clinical application.
      datePublished:2020-03-10T00:00:00Z
      dateModified:2021-06-25T00:00:00Z
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      pageEnd:1227
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      sameAs:https://doi.org/10.1007/s00262-020-02519-6
      keywords:
         Cyclin A1
         Epitope
         CD8 T cell
         HLA immunopeptidome
         Acute myeloid leukemia
         Ovarian carcinoma
         Oncology
         Immunology
         Cancer Research
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            name:Annika Nelde
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                     name:Department of Immunology, Interfaculty Institute of Cell Biology, University of Tübingen, Tübingen, Germany
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            name:German Cancer Research Center (DKFZ)
            address:
               name:German Cancer Research Center (DKFZ), Heidelberg, Germany
               type:PostalAddress
            type:Organization
      name:Juliane Sarah Walz
      affiliation:
            name:University of Tübingen
            address:
               name:Department of Hematology and Oncology, University of Tübingen, Tübingen, Germany
               type:PostalAddress
            type:Organization
            name:German Cancer Research Center (DKFZ)
            address:
               name:German Cancer Research Center (DKFZ), Heidelberg, Germany
               type:PostalAddress
            type:Organization
      name:Ulrich Keilholz
      affiliation:
            name:Charité Comprehensive Cancer Center
            address:
               name:Charité Comprehensive Cancer Center, Berlin, Germany
               type:PostalAddress
            type:Organization
            name:German Cancer Research Center (DKFZ)
            address:
               name:German Cancer Research Center (DKFZ), Heidelberg, Germany
               type:PostalAddress
            type:Organization
      name:Sebastian Ochsenreither
      affiliation:
            name:Charité Berlin
            address:
               name:Department of Hematology and Oncology, Campus Benjamin Franklin, Charité Berlin, Berlin, Germany
               type:PostalAddress
            type:Organization
            name:Charité Comprehensive Cancer Center
            address:
               name:Charité Comprehensive Cancer Center, Berlin, Germany
               type:PostalAddress
            type:Organization
            name:German Cancer Research Center (DKFZ)
            address:
               name:German Cancer Research Center (DKFZ), Heidelberg, Germany
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Hematology and Oncology, Campus Benjamin Franklin, Charité Berlin, Berlin, Germany
      name:Department of Hematology and Oncology, Campus Benjamin Franklin, Charité Berlin, Berlin, Germany
      name:Department of Hematology and Oncology, Campus Benjamin Franklin, Charité Berlin, Berlin, Germany
      name:Charité Comprehensive Cancer Center, Berlin, Germany
      name:German Cancer Research Center (DKFZ), Heidelberg, Germany
      name:Department of Immunology, Interfaculty Institute of Cell Biology, University of Tübingen, Tübingen, Germany
      name:Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), University Hospital Tübingen, Tübingen, Germany
      name:Department of Immunology, Interfaculty Institute of Cell Biology, University of Tübingen, Tübingen, Germany
      name:Immatics Biotechnologies GmbH, Tübingen, Germany
      name:Department of Hematology and Oncology, Campus Benjamin Franklin, Charité Berlin, Berlin, Germany
      name:German Cancer Research Center (DKFZ), Heidelberg, Germany
      name:Department of Hematology and Oncology, Campus Benjamin Franklin, Charité Berlin, Berlin, Germany
      name:German Cancer Research Center (DKFZ), Heidelberg, Germany
      name:Department of Hematology and Oncology, University of Tübingen, Tübingen, Germany
      name:German Cancer Research Center (DKFZ), Heidelberg, Germany
      name:Charité Comprehensive Cancer Center, Berlin, Germany
      name:German Cancer Research Center (DKFZ), Heidelberg, Germany
      name:Department of Hematology and Oncology, Campus Benjamin Franklin, Charité Berlin, Berlin, Germany
      name:Charité Comprehensive Cancer Center, Berlin, Germany
      name:German Cancer Research Center (DKFZ), Heidelberg, Germany

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