Notch agonists for the treatment of cancer

Patent metadata

Field	Value
Publication number	US-9683039-B2
Application number	US-201414212418-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 14, 2013
Publication date	Jun 20, 2017
Grant date	Jun 20, 2017

Abstract

The present invention is directed to methods of treating and preventing acute myeloid leukemia and acute myeloid leukemia relapse disease in a subject that involve administering a Notch receptor agonist.

First claim

What is claimed is:

1. A method of inducing cell differentiation and cell death in a population of acute myeloid leukemia leukemia-initiating cells (LICs), said method comprising:
administering a Notch receptor agonist to the population of acute myeloid leukemia LICs under conditions effective to induce cell differentiation and cell death in the population of acute myeloid leukemia LICs.

2. The method of claim 1 , wherein the population of acute myeloid leukemia LICs comprises a population of Lin − CD34 + acute myeloid leukemia cells.

3. The method of claim 1 , wherein the population of acute myeloid leukemia LICs comprises a population of Lin − CD34 + CD38 − acute myeloid leukemia cells.

4. The method of claim 1 , wherein the Notch receptor agonist is a Notch 1 receptor agonist, a Notch 2 receptor agonist, or a combination thereof.

5. The method of claim 1 , wherein the Notch receptor agonist is a Notch receptor-activating peptide ligand, or a Notch receptor agonist antibody or active binding fragment thereof.

6. The method of claim 1 , wherein the Notch receptor agonist is a Notch 2 receptor agonist antibody selected from the group consisting of an MHN2-25 antibody, an active binding fragment of the MHN2-25 antibody, an HMN2-29 antibody, and an active binding fragment of the HMN2-29 antibody.

7. The method of claim 1 , wherein said administering is carried out in vivo.

8. The method of claim 1 , wherein said administering is repeated periodically.

9. A method of treating acute myeloid leukemia in a subject, said method comprising:
selecting a subject having acute myeloid leukemia and
administering, to the selected subject, a Notch 2 receptor agonist, wherein said Notch 2 receptor agonist is an antibody or active binding fragment thereof that binds to the NRR or EGF domain of Notch 2, under conditions effective to treat the acute myeloid leukemia in the subject.

10. The method of claim 9 , wherein the Notch 2 receptor agonist antibody is selected from the group consisting of an MHN2-25 antibody, an active binding fragment of the MHN2-25 antibody, an HMN2-29 antibody, and an active binding fragment of the HMN2-29 antibody.

11. The method of claim 9 , wherein said administering is repeated periodically.

12. The method of claim 9 , wherein said administering is carried out in combination with another acute myeloid leukemia therapy.

13. The method of claim 12 , wherein the other acute myeloid leukemia therapy is selected from the group consisting of chemotherapy, stem cell transplantation therapy, a hypomethylating agent therapy, a FLT3 inhibitor therapy, a farnesyltransferase inhibitor therapy, and combinations thereof.

14. A method of inhibiting the development of acute myeloid leukemia relapse disease in a subject comprising:
selecting a subject having had acute myeloid leukemia and
administering, to the selected subject, a Notch receptor agonist under conditions effective to inhibit the development of acute myeloid leukemia relapse disease in the subject.

15. The method of claim 14 , wherein the selected subject is in complete remission of acute myeloid leukemia.

16. The method of claim 14 , wherein the selected subject has a measurable amount of minimal residual disease.

17. The method of claim 14 , wherein the Notch receptor agonist is a Notch 1 receptor agonist, a Notch 2 receptor agonist, or a combination thereof.

18. The method of claim 14 , wherein the Notch receptor agonist is a Notch receptor-activating peptide ligand or a Notch receptor agonist antibody or active binding fragment thereof.

19. The method of claim 14 , wherein the Notch receptor agonist is a Notch 2 receptor agonist antibody selected from the group consisting of an MHN2-25 antibody, an active binding fragment of the MHN2-25 antibody, an HMN2-29 antibody, and an active binding fragment of the HMN2-29 antibody.

20. The method of claim 14 , wherein said administering is carried out in combination with another acute myeloid leukemia therapy.

21. The method according to claim 20 , wherein the other acute myeloid leukemia therapy is selected from the group consisting of chemotherapy, stem cell transplantation therapy, a hypomethylating agent therapy, a FLT3 inhibitor therapy, a farnesyltransferase inhibitor therapy, and combinations thereof.

Assignees

• Aifantis Iannis
• Lobry Camille
• Univ New York

Inventors

• Aifantis Iannis
• Lobry Camille

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/28 Primary

  against receptors, cell surface antigens or cell surface determinants · CPC title

• A61K38/17

  from animals; from humans {(enzyme inhibitors A61K38/005)} · CPC title

• C07K16/24

  against cytokines, lymphokines or interferons · CPC title

• C07K14/705

  Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} · CPC title