title: Targeting c-MYC with T-cells.
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 H2(b) 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.
authors.affiliation: Department of Immunology, Charité Berlin, Berlin, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Helm
authors.forename: Thomas
authors.initials: T
authors.lastname: Kammertoens
authors.forename: Frank M
authors.initials: FM
authors.lastname: Lehmann
authors.forename: Andrea
authors.initials: A
authors.lastname: Wilke
authors.forename: Heiko
authors.initials: H
authors.lastname: Bruns
authors.forename: Josef
authors.initials: J
authors.lastname: Mautner
authors.forename: Georg W
authors.initials: GW
authors.lastname: Bornkamm
authors.forename: Armin
authors.initials: A
authors.lastname: Gerbitz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008223:Lymphoma / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D014611:Vaccination
chemical_list: D018984:Epitopes, T-Lymphocyte; C000715470:MAS1 protein, human; C489427:MYC protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D007371:Interferon-gamma