IMMUNE-CHECKPOINT INHIBITORS FOR USE IN THE TREATMENT OF BLOOD-BORNE CANCERS

• US 20170037133A1
• Filed: 08/05/2016
• Published: 02/09/2017
• Est. Priority Date: 08/05/2015
• Status: Abandoned Application

• Current Assignee: Amgen Research (Munich) GmbH (Amgen Inc.)
• Original Assignee: Amgen Research (Munich) GmbH (Amgen Inc.)
• Inventors: Fiedler, Walter, Wellbrock, Jasmin, Stamm, Hauke, Klingler, Felix
• Application Number:
  US15/229,438
• Publication Number:
  US 20170037133A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2239/48 Blood cells, e.g. leukemia or lymphoma
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4631 Chimeric Antigen Receptors [CAR]
• CPC Class Codes: A61K 39/464499 Undefined tumor antigens, e.g. tumor lysate or antigens targeted by cells isolated from tumor
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/2851 against the lectin superfamily, e.g. CD23, CD72
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/62 comprising only variable region components
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2319/74 : containing a fusion for binding to a cell surface receptor
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides an inhibitor against CD112 (Nectin-2, PVRL2), CD155 (PVR), Galectin-9, TIM-3 and/or TIGIT for use in a method of treatment of a blood-borne cancer, in particular acute myeloid leukemia (AML). Moreover, the present invention provides a pharmaceutical composition comprising an inhibitor against CD112 (Nectin-2, PVRL2), CD155 (PVR), Galectin-9, TIM-3 and/or TIGIT and a CAR T cell. The present invention further provides a pharmaceutical composition comprising an inhibitor against CD112 (Nectin-2, PVRL2), CD155 (PVR), Galectin-9, TIM-3 and/or TIGIT and an antibody construct that is capable of engaging T cells.

Claims

1. A method of treating a blood-borne cancer in a subject suffering therefrom comprising administering to the subject an effective amount of an inhibitor of CD112 (Nectin-2, PVRL2), CD155 (PVR), Galectin-9, TIM-3 and/or TIGIT.

2. The method according to claim 1, wherein said inhibitor of CD112 inhibits the interaction between CD112 and TIGIT.

3. The method according to claim 1, wherein said inhibitor of CD155 inhibits the interaction between CD155 and TIGIT.

4. The method according to claim 1, wherein said inhibitor of TIGIT inhibits the interaction between TIGIT and CD112.

5. The method according to claim 1, wherein said inhibitor of TIGIT inhibits the interaction between TIGIT and CD155.

6. The method according to claim 1, wherein said inhibitor of Galectin-9 inhibits the interaction between Galectin-9 and TIM-3.

7. The method according to claim 1, wherein said inhibitor of TIM-3 inhibits the interaction between TIM-3 and Galectin-9.

8. The method according to claim 1, wherein the inhibitor is an antibody construct.

9. The method according to claim 1, further comprising administering a CAR T cell or an antibody construct.

10. The method according to claim 8 or 9, wherein the antibody construct engages T cells.

11. The method according to claim 1, further comprising administering an immunostimulant.

12. The method according to claim 10, wherein said antibody construct comprises a CD3 binding domain and a further binding domain targeting a surface molecule expressed on a cancer cell.

13. The method according to claim 12, wherein said surface molecule is CD33, CD19, or Flt3.

14. The method according to claim 10, wherein said antibody construct also binds CD3epsilon.

15. The method according to claim 1, wherein said inhibitor of CD112 reduces expression of CD112.

16. The method according to claim 1, wherein said inhibitor of CD155 reduces expression of CD155.

17. The method according to claim 1, wherein said inhibitor of TIGIT reduces expression of TIGIT.

18. The method according to claim 1, wherein said inhibitor of Galectin-9 reduces expression of Galectin-9.

19. The method according to claim 1, wherein said inhibitor of TIM-3 reduces expression of TIM-3.

20. The method according to claim 1, wherein said inhibitor is an interfering RNA (iRNA).

32. The method according to claim 1, wherein the blood-borne cancer is acute myeloid leukemia (AML).

21. A method of treating a blood-borne cancer in a subject suffering therefrom comprising knocking out CD112 (Nectin-2, PVRL2), CD155 (PVR), TIGIT, Galectin-9 and/or TIM-3 on cancer cells in the subject.

22. The method of claim 21, wherein said knocking out is achieved by using a CRISPR/cas9 technique.

33. The method according to claim 21, wherein the blood-borne cancer is acute myeloid leukemia (AML).

23-32. -32. (canceled)