Method for Treating and Diagnosing Hematologic Malignancies

• US 20110177088A1
• Filed: 08/14/2008
• Published: 07/21/2011
• Est. Priority Date: 08/17/2007
• Status: Active Grant

• Current Assignee: Universite de la Mediterranee
• Original Assignee: Universite de la Mediterranee
• Inventors: Olive, Daniel, Truhneh, Alemseged, Xerri, Luc
• Granted Patent: US 9,243,052 B2
• Time in Patent Office: Days
• US Class Current: 424/144.1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07K 14/4747 Apoptosis related proteins
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: G01N 33/57426 leukemia

Abstract

The invention relates to methods for treating and diagnosing hematologic malignancies, Chronic lymphocytic leukemia and Small Lymphocytic Lymphoma in particular, using PD-1 ligands (PD-L1, PD-L2 or anti-PD-1 antibodies).

Claims

1. A method for treating a hematologic malignancy, comprising the use of a ligand of PD1, wherein said ligand of PD1 is selected from the group consisting of PD-L1 or a fragment thereof which binds to PD1, PD-L2 or a fragment thereof which binds to PD1, and an anti-PD1 antibody or a fragment thereof which binds to PD1, and wherein the hematologic malignancy is selected from the group consisting of a chronic lymphocytic leukemia of B-cell origin, a small lymphocytic lymphoma of B-cell origin, a multiple myeloma, an acute B cell leukemia and a mantle cell lymphoma.

3. The method according to claim 1, wherein the hematologic malignancy is a chronic lymphocytic leukemia of B-cell origin or a small lymphocytic lymphoma of B-cell origin.

4. The method according to claim 1 or 3, wherein said ligand of PD1 is PD-L1 or PD-L2.

5. The method according to claim 1 or 3, wherein said ligand of PD1 is an anti-PD1 antibody or a fragment thereof which binds to PD1.

6. The method according to claim 5, wherein said anti-PD1 antibody or said fragment thereof induces death and/or elimination of a B-cell expressing PD1.

7. The method according to claim 5, wherein said ligand of PD1 is a monoclonal antibody.

8. The method according to claim 5, wherein said ligand of PD1 is a monoclonal antibody obtainable from a hybridoma deposited at the COLLECTION NATIONALE DE CULTURES DE MICROORGANISMES (CNCM) under the number CNCM I-3745.

9. The method according to claim 5, wherein said antibody or fragment thereof displays the same antigen combining sites as an antibody obtainable by the hybridoma deposited at the CNCM under the number CNCM I-3745.

2. (canceled)

10. (canceled)

11. A hybridoma cell line suitable for obtaining anti-PD1 monoclonal antibodies which induce death and/or elimination of a B-cell expressing PD1.

12. A hybridoma cell line deposited at the CNCM under the number CNCM I-3745.

16. A monoclonal antibody obtained from a hybridoma of claim 12.

13. An anti-PD1 antibody or a fragment thereof which binds to PD1, wherein said antibody or said fragment induces death and/or elimination of a B-cell expressing PD1.

14. An anti-PD1 antibody or a fragment of claim 13, wherein said B-cell is a chronic lymphocytic leukemia B-cell and/or of a small lymphocytic lymphoma B-cell.

15. An anti-PD1 antibody according to claim 13, wherein said antibody is a monoclonal antibody.

17. An anti-PD1 antibody or a fragment thereof which binds to PD1, wherein said antibody or fragment displays the same antigen combining sites as the antibody obtainable by the hybridoma deposited at the CNCM under the number CNCM I-3745.

18. A method for the detection of a B cell selected from the group consisting of a chronic lymphocytic leukemia B-cell, a small lymphocytic lymphoma B-cell, a multiple myeloma B cell, an acute leukemia B cell and a mantle cell lymphoma B cell, comprising the use of an anti-PD1 antibody or a fragment thereof which binds to PD1.

19. A method for diagnosing in a subject a hematologic malignancy selected from the group consisting of a chronic lymphocytic leukemia of B-cell origin, a small lymphocytic lymphoma of B-cell origin, a multiple myeloma, an acute B cell leukemia and a mantle cell lymphoma, comprising the use of an anti-PD1 antibody or a fragment thereof which binds to PD1.

20-21. -21. (canceled)