Antibodies directed against ICOS and uses thereof

Patent metadata

Field	Value
Publication number	US-10633446-B2
Application number	US-201916452984-A
Country	US
Kind code	B2
Filing date	Jun 26, 2019
Priority date	Mar 31, 2011
Publication date	Apr 28, 2020
Grant date	Apr 28, 2020

Abstract

The present invention provides antibodies directed against ICOS or a derivative thereof which neutralize ICOS engagement on Treg by inhibiting the fixation between ICOS and ICOS-L and abrogate proliferation of Treg induced by plasmacytoid dendritic cells. The present invention further provides antibodies directed against ICOS or a derivative thereof which induce IL-10 and IFNγ production, induce CD4− T cells proliferation, reduce Tconv proliferation, and increase the immunosuppressive function of Treg.

First claim

The invention claimed is:

1. A method of treatment of cancer in a patient in need thereof, wherein said cancer is determined to have regulatory T cells (Treg cells) present in a tumor microenvironment, the method comprising administering to the patient an antibody directed against human Inducible T-cell costimulator (ICOS), wherein said antibody reduces the number and/or activity of Treg cells in a tumor microenvironment.

2. The method of claim 1 , wherein said antibody binds human ICOS with an ED50 of less than about 10 μg/ml, less than about 5 μg/ml, less than about 1 μg/ml, less than about 0.5 μg/ml, or less than about 0.1 μg/ml, wherein the ED50 is a concentration of antibody at which 50% of ICOS binding sites are saturated as measured by flow cytometry.

3. The method of claim 1 , wherein said antibody reduces the number of Treg cells in a tumor microenvironment.

4. The method of claim 1 , wherein said antibody reduces the activity of Treg cells in a tumor microenvironment.

5. The method of claim 1 , wherein the cancer is human malignant lymphoma.

6. The method of claim 1 , wherein said cancer is ovarian cancer.

7. The method of claim 1 , wherein said cancer is cervical cancer.

8. The method of claim 1 , wherein said cancer is breast cancer.

9. The method of claim 1 , wherein said cancer is colon cancer.

10. The method of claim 1 , wherein said cancer is lung cancer.

11. The method of claim 1 , wherein said cancer is prostate cancer.

12. The method of claim 1 , wherein said cancer is head and neck cancer.

13. The method of claim 1 , wherein said cancer is pancreatic cancer.

14. The method of claim 1 , wherein said cancer is bladder cancer.

15. The method of claim 1 , wherein said cancer is colorectal cancer.

16. The method of claim 1 , wherein said cancer is kidney cancer.

17. The method of claim 1 , wherein said cancer is stomach cancer.

18. The method of claim 1 , wherein said cancer is skin cancer.

19. The method of claim 1 , wherein said cancer is esophageal cancer.

20. The method of claim 2 , wherein the flow cytometry is performed using stable transfectants expressing ICOS.

Assignees

• Inst Nat Sante Rech Med
• Inst Jean Paoli & Irene Calmettes
• Univ Aix Marseille
• Univ Claude Bernard Lyon
• Centre Leon Berard
• Inserm Institut National De La Santeet De La Rech Medicale
• Univ Marseille
• Univ Claude Bernerd—Lyon

Inventors

• Faget Julien
• Caux Christophe
• Menetrier-Caux Christine
• Nunes Jacques
• Olive Daniel

Classifications

• C07K16/2818 Primary

  against CD28 or CD152 · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• G01N33/56972

  White blood cells · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61K2039/505

  comprising antibodies · CPC title