Antibodies targeting human IL1RAP (IL1R3) show therapeutic effects in xenograft models of acute myeloid leukemia.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


title = "Antibodies targeting human IL1RAP (IL1R3) show therapeutic effects in xenograft models of acute myeloid leukemia.",
abstract = "Acute myeloid leukemia (AML) is associated with a poor survival rate, and there is an urgent need for novel and more efficient therapies, ideally targeting AML stem cells that are essential for maintaining the disease. The interleukin 1 receptor accessory protein (IL1RAP; IL1R3) is expressed on candidate leukemic stem cells in the majority of AML patients, but not on normal hematopoietic stem cells. We show here that monoclonal antibodies targeting IL1RAP have strong antileukemic effects in xenograft models of human AML. We demonstrate that effector-cell-mediated killing is essential for the observed therapeutic effects and that natural killer cells constitute a critical human effector cell type. Because IL-1 signaling is important for the growth of AML cells, we generated an IL1RAP-targeting antibody capable of blocking IL-1 signaling and show that this antibody suppresses the proliferation of primary human AML cells. Hence, IL1RAP can be efficiently targeted with an anti-IL1RAP antibody capable of both achieving antibody-dependent cellular cytotoxicity and blocking of IL-1 signaling as modes of action. Collectively, these results provide important evidence in support of IL1RAP as a target for antibody-based treatment of AML.",
author = "Helena {\AA}gerstam and Christine Karlsson and Nils Hansen and Carl Sand{\'e}n and Maria Askmyr and {von Palffy}, Sofia and Carl H{\"o}gberg and Marianne Rissler and Mark Wunderlich and Gunnar Juliusson and Johan Richter and Kjell Sj{\"o}str{\"o}m and Ravi Bhatia and Mulloy, {James C} and Marcus J{\"a}r{\aa}s and Thoas Fioretos",
year = "2015",
doi = "10.1073/pnas.1422749112",
language = "English",
volume = "112",
pages = "10786--10791",
journal = "Proceedings of the National Academy of Sciences",
issn = "1091-6490",
publisher = "National Acad Sciences",
number = "34",