<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Antigen-armed antibodies (AgAbs) in the treatment of Acute Myeloid Leukemia (AML)"^^ . "Acute myeloid leukemia (AML) accounts for 80% of acute leukemia cases in adults and results from the accumulation of immature malignant myeloid progenitor cells at the expense of healthy differentiated counterparts. These cells invade the bone marrow, the blood and can also infiltrate organs in the periphery. While recent progresses in AML management moderately improved the survival of patients below the age of 65, about 70% of older patients succumb to the disease within one year after diagnosis. Therefore, the search for more therapeutic options in AML is imperative. In this doctoral work, a novel approach based on the AML-specific antibodies designed to deliver immunodominant Epstein-Barr virus (EBV) epitopes to AML tumour cells is assessed. These antigen-armed antibodies (AgAbs) target surface markers upregulated on AML cells, namely CD33, CD123, CLL-1 and FR-b. After receptor-mediated endocytosis, the viral epitopes included in the AgAbs are shuttled into the endosomal compartments of the target cells, where the epitopes can be processed for MHC class II-restricted presentation on the cell surface. In EBV-positive individuals (95% of the human population worldwide), circulating memory virus-specific cytotoxic CD4+ T cells can recognize the MHCII-bound peptides and mediate cell lysis. This strategy aims at boosting the low basal immunogenicity of AML blasts in order to redirect a potent anti-viral immunity toward these cancer cells. In vitro experiments with multiple AML cell lines demonstrated the potency of AgAbs to target the aforementioned surface marker, culminating in the presentation of epitopes at the cell surface. This led to a strong EBV-specific CD4+ T cell activation, characterized by IFNg and granzyme B secretion. These activated T cells were also capable of directly eliminating AgAb-treated AML cell line cells. Furthermore, AgAb-mediated T cell activation was shown to eliminate bystander malignant cells, probably through IFNg and TNF-a signaling. Ex vivo experiments with AgAbs showed a promising potential to stimulate EBV-specific memory CD4+ T cells from AML patients. Upon AgAb treatment, these cells proliferated and killed a substantial proportion of patient blasts. Finally, a murine model of AML was developed. AgAbs fused to murine cytomegalovirus epitopes potently expanded murine CD4+ T cells in vivo, culminating in a prolonged survival in AgAb-treated tumour-bearing mice.\r\nAltogether, the promising results from this study demonstrate the potential of AgAbs to redirect endogenous CD4+ cytotoxic T cells against AML cells loaded with EBV antigens, paving the way for future studies and clinical trials."^^ . "2023" . . . . . . . "Guillaume Emmanuel"^^ . "Wassmer"^^ . "Guillaume Emmanuel Wassmer"^^ . . . . . . "Antigen-armed antibodies (AgAbs) in the treatment of Acute Myeloid Leukemia (AML) (PDF)"^^ . . . "Thesis GW F100.pdf"^^ . . . "Antigen-armed antibodies (AgAbs) in the treatment of Acute Myeloid Leukemia (AML) (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Antigen-armed antibodies (AgAbs) in the treatment of Acute Myeloid Leukemia (AML) (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Antigen-armed antibodies (AgAbs) in the treatment of Acute Myeloid Leukemia (AML) (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Antigen-armed antibodies (AgAbs) in the treatment of Acute Myeloid Leukemia (AML) (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Antigen-armed antibodies (AgAbs) in the treatment of Acute Myeloid Leukemia (AML) (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #33372 \n\nAntigen-armed antibodies (AgAbs) in the treatment of Acute Myeloid Leukemia (AML)\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .