Targeting c-MYC with T-Cells |
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| Authors: | Florian Helm Thomas Kammertoens Frank M. Lehmann Andrea Wilke Heiko Bruns Josef Mautner Georg W. Bornkamm Armin Gerbitz |
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| Affiliation: | 1. Department of Immunology, Charité Berlin, Berlin, Germany.; 2. Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Center, Munich, Munich, Germany.; 3. Department of Pediatrics, Technical University (TU) Munich and Clinical Cooperation Group Pediatric Tumor Immunology, TU Munich and Helmholtz Center, Munich, Germany.; 4. Department of Hematology, Oncology, University of Erlangen, Erlangen, Germany .; University of Illinois at Chicago, United States of America, |
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| Abstract: | Over-expression of the proto-oncogene c-MYC is frequently observed in a variety of tumors and is a hallmark of Burkitt´s lymphoma. The fact that many tumors are oncogene-addicted to c-MYC, renders c-MYC a powerful target for anti-tumor therapy. Using a xenogenic vaccination strategy by immunizing C57BL/6 mice with human c-MYC protein or non-homologous peptides, we show that the human c-MYC protein, despite its high homology between mouse and man, contains several immunogenic epitopes presented in the context of murine H2b haplotype. We identified an MHC class II-restricted CD4+ T-cell epitope and therein an MHC class I-restricted CD8+ T-cell epitope (SSPQGSPEPL) that, after prime/boost immunization, protected up to 25% of mice against a lethal lymphoma challenge. Lymphoma-rejecting animals contained MHC multimer-binding CD8+ cell within the peripheral blood and displayed in vivo cytolytic activity with specificity for SSPQGSPEPL. Taken together these data suggest that oncogenic c-MYC can be targeted with specific T-cells. |
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