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.
| Original language | English |
|---|---|
| Journal | Blood |
| Volume | 121 |
| Issue number | 18 |
| Pages (from-to) | 3709-13 |
| Number of pages | 5 |
| ISSN | 0006-4971 |
| DOIs | |
| Publication status | Published - 2 May 2013 |
| Externally published | Yes |
Keywords
- Adult
- Aged
- Aged, 80 and over
- Antibodies/pharmacology
- Antibody Specificity
- Cells, Cultured
- Cytotoxicity, Immunologic/drug effects
- Female
- Humans
- Immunotherapy/methods
- Interleukin-1 Receptor Accessory Protein/antagonists & inhibitors
- Leukemia, Myeloid, Acute/pathology
- Male
- Middle Aged
- Molecular Targeted Therapy
- Neoplastic Stem Cells/drug effects