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Selective killing of candidate AML stem cells by antibody targeting of IL1RAP.

Authors
  • Askmyr, Maria
  • Ågerstam, Helena
  • Hansen, Nils
  • Gordon, Sandra
  • Arvanitakis, Alexandros
  • Rissler, Marianne
  • Juliusson, Gunnar
  • Richter, Johan
  • Järås, Marcus
  • Fioretos, Thoas
Type
Published Article
Journal
Blood
Publisher
American Society of Hematology
Publication Date
May 02, 2013
Volume
121
Issue
18
Pages
3709–3713
Identifiers
DOI: 10.1182/blood-2012-09-458935
PMID: 23479569
Source
Medline
License
Unknown

Abstract

IL1RAP, a co-receptor for interleukin (IL)-1 and IL-33 receptors, was previously found to be highly upregulated on candidate chronic myeloid leukemia stem cells, allowing for leukemia-selective killing using IL1RAP-targeting antibodies. We analyzed IL1RAP expression in a consecutive series of 29 patients with acute myeloid leukemia (AML) and, based on the level of expression in mononuclear cells (MNCs), we divided the samples into 3 groups: IL1RAP low (n = 6), IL1RAP intermediate (n = 11), and IL1RAP high (n = 12). Within the CD34+CD38- population, the intermediate and high groups expressed higher levels of IL1RAP than did corresponding normal cells. With the aim to target AML stem cells, an anti-IL1RAP monoclonal antibody was generated followed by isotype switching for improved antibody-dependent, cell-mediated cytotoxicity activity. Using this antibody, we achieved selective killing of AML MNC, CD34+CD38+, and CD34+CD38- cells. Our findings demonstrate that IL1RAP is a promising new therapeutic target in AML.

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