METHODS FOR PROMOTING T CELLS RESPONSE

• US 20190309075A1
• Filed: 10/20/2017
• Published: 10/10/2019
• Est. Priority Date: 10/21/2016
• Status: Active Grant

• Current Assignee: Inserm (institut national de la sant et de la recherche mdicale, Nantes Universite, OSE Immunotherapeutics
• Original Assignee: Inserm (institut national de la sant et de la recherche mdicale, OSE Immunotherapeutics, Universite De Nantes
• Inventors: CHIFFOLEAU, Elise, TEPPAZ, Geraldine, POIRIER, Nicolas, VANHOVE, Bernard, GAUTTIER, Vanessa
• Granted Patent: US 11,365,257 B2
• Time in Patent Office: Days
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/4726 Lectins
• CPC Class Codes: C07K 14/7056 Lectin superfamily, e.g. CD23, CD72
• CPC Class Codes: C07K 16/2851 against the lectin superfamily, e.g. CD23, CD72
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C12N 15/115 Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers

Abstract

The present invention relates to methods for promoting T cells response. The inventors examined the expression and function of CLEC-1 in human DCs and demonstrated for the first time a cell-surface expression. They investigated its functional role following triggering on orchestration of T-cell responses. The inventors showed in vitro and in vivo with CLEC-1 deficient rats and rat CLEC-1 Fc fusion protein that disruption of CLEC-1 signalling enhances in vitro Th17 activation and in vivo enhances T cell priming and Th17 and Th1 activation. In particular, the present invention relates to CLEC-1 antagonists for promoting T cells response in a subject in need thereof.

Claims

1. A method of promoting T cells response in a human subject suffering from cancer, comprising administering to the subject a therapeutically effective amount of an antagonist of human CLEC-1.

3. The method of claim 1 wherein the subject suffers from a cancer selected from the group consisting of bile duct cancer, bladder cancer, bone cancer, brain and central nervous system cancer, breast cancer, Castleman disease cervical cancer, colorectal cancer, endometrial cancer, esophagus cancer, gallbladder cancer, gastrointestinal carcinoid tumors, Hodgkin'"'"'s disease, non-Hodgkin'"'"'s lymphoma, Kaposi'"'"'s sarcoma, kidney cancer, laryngeal and hypopharyngeal cancer, liver cancer, lung cancer, mesothelioma, plasmacytoma, nasal cavity and paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, oral cavity and oropharyngeal cancer, ovarian cancer, pancreatic cancer, penile cancer, pituitary cancer, prostate cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, skin cancer, stomach cancer, testicular cancer, thymus cancer, thyroid cancer, vaginal cancer, vulvar cancer, and uterine cancer.

4. The method according to claim 1, wherein the antagonist of human CLEC-1 is a small organic molecule.

5. The method according to claim 1, wherein the antagonist of CLEC-1 is an antibody or an antigen-binding fragment thereof.

6. The method of claim 5, wherein the antagonist of human CLEC-1 is selected from the group consisting of chimeric antibodies, humanized antibodies and fully human monoclonal antibodies.

7. The method of claim 5 wherein the antibody or antigen-binding fragment thereof specifically binds to the extracellular domain of human CLEC-1.

8. The method according to claim 1, wherein the antagonist of human CLEC-1 is a polypeptide.

9. The method according to claim 8 wherein the polypeptide is a functional equivalent of human CLEC-1.

10. The method according to claim 9 wherein the polypeptide is a functional equivalent of human CLEC-1 fused to an immunoglobulin constant domain.

11. The method according to claim 1, wherein the antagonist of human CLEC-1 is an aptamer.

13. The method according to claim 1, wherein the antagonist of human CLEC-1 is used in combination with a conventional treatment.

14. The method according to according to claim 1, wherein the antagonist of human CLEC-1 is used in combination with a chemotherapeutic agent, a targeted cancer therapy, an immunotherapeutic agent or radiotherapy.

2. (canceled)

12. A method of treating cancer by promoting a T cell response in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an antagonist of human CLEC-1.

17. The method according to claim 12, wherein the antagonist of human CLEC-1 is used in combination with a conventional treatment.

18. The method according to according to claim 12, wherein the antagonist of human CLEC-1 is used in combination with a chemotherapeutic agent, a targeted cancer therapy, an immunotherapeutic agent or radiotherapy.

15. (canceled)

16. (canceled)