TIM-3 ligands and methods of modulating immune responses

Patent metadata

Field	Value
Publication number	US-9346876-B2
Application number	US-201414264791-A
Country	US
Kind code	B2
Filing date	Apr 29, 2014
Priority date	Oct 3, 2003
Publication date	May 24, 2016
Grant date	May 24, 2016

Abstract

The invention relates to isolated polypeptides and nucleic acids encoding polypeptides which comprise a tim-3 IgV domain and a tim-3 intracellular domain, wherein the polypeptides do not comprise a tim-3 mucin domain or a tim-3 transmembrane domain. In addition, the invention relates to methods of modulating immune responses in a subject, comprising administering to the subject a therapeutically effective amount of an agent that modulates tim-3 activity. Immune responses include, but are not limited to, immune tolerance, transplantation tolerance, Th1 responses and Th2 responses.

First claim

We claim:

1. A method for increasing a Th1-mediated immune response in a subject, the method comprising administering an antibody or antigen-binding fragment thereof that binds to a galectin-9 polypeptide and decreases T cell Immunoglobulin and Mucin domain containing molecule-3 (tim-3) activity, thereby increasing a Th1-mediated immune response in the subject.

2. The method of claim 1 , wherein the subject is afflicted with a hyperplastic condition.

3. The method of claim 2 , wherein the hyperplastic condition is renal cell cancer, Kaposi's sarcoma, chronic leukemia, prostate cancer, breast cancer, sarcoma, pancreatic cancer, leukemia, ovarian carcinoma, rectal cancer, throat cancer, melanoma, colon cancer, bladder cancer, lymphoma, mastocytoma, lung cancer, mammary adenocarcinoma, pharyngeal squamous cell carcinoma, testicular cancer, gastrointestinal cancer, stomach cancer, Hodgkin's lymphoma, or a combination thereof.

4. The method of claim 1 , wherein the subject is afflicted with a Th2-mediated disorder.

5. The method of claim 4 , wherein the Th2-mediated disorder is asthma, an allergy, allergic rhinitis, gastrointestinal allergy, food allergy, eosinophilia, conjunctivitis, or glomerulonephritis.

6. The method of claim 1 , wherein the galectin-9 polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 10, or SEQ ID NO: 19.

7. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof inhibits binding of (i) a polypeptide comprising amino acids 30-128 of SEQ ID NO: 13 to (ii) the galectin-9 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 10 or SEQ ID NO: 19.

Assignees

• Brigham & Womens Hospital
• Beth Israel Hospital

Inventors

• Kuchroo Vijay K
• Strom Terry Barton
• Cha Eugene K
• Chakravarti Sumone
• Sabatos-Peyton Catherine Anne
• Zhu Chen
• Zheng Xin Xiao
• Sanchez-Fueyo Alberto

Classifications

• A61P7/06

  Antianaemics · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title