Methods related to TIM 3, a Th1-specific cell surface molecule, for activating antigen presenting cells

• US 9,333,256 B2
• Filed: 08/20/2014
• Issued: 05/10/2016
• Est. Priority Date: 01/30/2002
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated, Dana-Farber Cancer Institute
• Original Assignee: Brigham and Women's Hospital Incorporated, Dana-Farber Cancer Institute
• Inventors: Kuchroo, Vijay K., Monney, Laurent, Gaglia, Jason L., Greenfield, Edward A., Freeman, Gordon J., Waldner, Hanspeter
• Primary Examiner(s): Kim, Yunsoo
• Application Number:
  US14/464,447
• Publication Number:
  US 20150044230A1
• Time in Patent Office: 629 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/50 characterized by immunoglobulin fragments

Abstract

The present invention provides compositions and methods useful for promoting or reducing T-cell trafficking to a target tissue. Also provided are compositions and methods useful for promoting or inhibiting antigen-presenting cell (APC) activation. The invention is related to discovery of functional characteristics of TIM-3, a molecule that is preferentially expressed on the surface of Th1 cells. The methods are useful for treating disorders including cancer, infectious disease, allergy, asthma, and autoimmune disease.

Claims

1. A method for treating a subject having cancer, the method comprising administering a TIM-3 (T cell Immunoglobulin and Mucin domain containing molecule-3) binding molecule in an amount effective to promote T-cell trafficking to a target tissue, wherein the TIM-3 binding molecule is a TIM-3 antibody or antigen-binding fragment thereof, in combination with a chemotherapeutic agent, thereby treating the cancer.

2. The method of claim 1, wherein the chemotherapeutic agent is directly toxic to cancer cells.

3. The method of claim 2, wherein the chemotherapeutic agent is an alkylating/alkaloid agent.

4. The method of claim 3, wherein the alkylating/alkaloid agent comprises a nitrogen mustard.

5. The method of claim 4, wherein the nitrogen mustard is selected from the group consisting of:

mechlorethamin HCl, chlorambucil, and ifosfamide.

6. The method of claim 3, wherein the alkylating/alkaloid agent is selected from the group consisting of:

cisplatin, carboplatin, carmustine, lomustine, streptozocin, busulfan, procarbozine, and temozolomide.

7. The method of claim 2, wherein the chemotherapeutic agent is selected from the group consisting of:

busulfan, capecitabine, carboplatin, carmustaine, chlorambucil, cisplatin, cladribine, cytarabine HCl, daunorubicine HCl, doxorubicin, epirubicin, etoposide, fludarabine, fluorouracil (5-FU), gemcitabine, ifosfamide, irinotecan, lomustine (CCNU), mechlorethamine HCl (nitrogen mustard), mercaptopurine, mitoxantrone, mitoxantrone HCl, paclitaxel, pentostatin, plicamycin, semustine, streptozocin, taxane analog, temozolomide, teniposide (VM-26), thioguanine, vinblastine sulfate, and vindesine sulfate.

8. The method of claim 1, wherein the TIM-3 antibody or antigen-binding fragment thereof binds to an extracellular region of TIM-3.

9. The method of claim 1, wherein the TIM-3 antibody or antigen-binding fragment thereof is administered directly to the target tissue.

10. The method of claim 1, wherein the TIM-3 antibody or antigen-binding fragment thereof is administered intravenously.