Method of treatment for leukemia using an anti-IL1RAP antibody
The present invention provides agents comprising or consisting of a binding moiety with specificity for interleukin-1 receptor accessory protein (IL1RAP) for use in inducing cell death and/or inhibiting the growth and/or proliferation of pathological stem cells and/or progenitor cells associated with a neoplastic hematologic disorder, wherein the cells express IL1RAP. A related aspect of the invention provides agents comprising or consisting of a binding moiety with specificity for interleukin-1 receptor accessory protein (IL1RAP) for use in detecting pathological stem cells and/or progenitor cells associated with a neoplastic hematologic disorder, wherein the cells express IL1RAP. Further provided are pharmacological compositions comprising the agents of the invention and methods of using the same.
1. A method of treatment of leukemia, the method comprising administering a therapeutically effective amount of an antibody with specificity for an extracellular domain of the interleukin-1 receptor accessory protein (IL1RAP),
wherein the antibody induces antibody-dependent cell-mediated cytotoxicity (ADCC) of pathological stem cells and/or progenitor cells expressing IL1RAP and being associated with the leukemia;
wherein the antibody inhibits IL1RAP binding activity associated signaling on pathological stem cells and/or progenitor cells expressing IL1RAP.
2. The method according to claim 1 , wherein the pathological stem cells and/or progenitor cells comprise a BCR/ABL1 fusion gene.
3. The method according to claim 1 , wherein the leukemia is selected from the group consisting of chronic myeloid leukemia (CML), myeloproliferative disorders (MPD), myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).
4. The method according to claim 1 , wherein the leukemia is CML.
5. The method according to claim 1 , wherein the leukemia is MDP.
6. The method according to claim 1 , wherein the leukemia is MDS.
7. The method according to claim 1 , wherein the leukemia is ALL.
8. The method according to claim 1 , wherein the leukemia is AML.
9. The method according to claim 1 , wherein the pathological stem cells and/or progenitor cells comprise a Ph chromosome.
10. The method according to claim 1 , wherein the antibody blocks binding of one or more co-receptors to IL1RAP.
11. The method according to claim 10 , wherein the one or more co-receptors are selected from the group consisting of IL1R1, ST2, C-KIT and IL1RL2.
12. The method according to claim 1 , wherein the antibody induces apoptosis of the stem cells and/or progenitor cells.
13. The method according to claim 1 , wherein the antibody further comprises a cytotoxic moiety.
14. The method according to claim 1 , wherein the antibody blocks binding of IL1R1.