title: Selective killing of candidate AML stem cells by antibody targeting of IL1RAP.
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.
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Lund University, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Askmyr
authors.forename: Helena
authors.initials: H
authors.lastname: Ågerstam
authors.forename: Nils
authors.initials: N
authors.lastname: Hansen
authors.forename: Sandra
authors.initials: S
authors.lastname: Gordon
authors.forename: Alexandros
authors.initials: A
authors.lastname: Arvanitakis
authors.forename: Marianne
authors.initials: M
authors.lastname: Rissler
authors.forename: Gunnar
authors.initials: G
authors.lastname: Juliusson
authors.forename: Johan
authors.initials: J
authors.lastname: Richter
authors.forename: Marcus
authors.initials: M
authors.lastname: Järås
authors.forename: Thoas
authors.initials: T
authors.lastname: Fioretos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000494:pharmacology*; D000918:Antibody Specificity; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D053577:Interleukin-1 Receptor Accessory Protein / Q000037:antagonists & inhibitors / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology
chemical_list: D000906:Antibodies; C507765:IL1RAP protein, human; D053577:Interleukin-1 Receptor Accessory Protein