Agents that modulate immune cell activation and methods of use thereof

• US 20030232323A1
• Filed: 11/12/2002
• Published: 12/18/2003
• Est. Priority Date: 11/13/2001
• Status: Abandoned Application

• Current Assignee: Brigham and Women's Hospital Incorporated, Dana-Farber Cancer Institute
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: Buhlmann, Janet, Freeman, Gordon J., Sharpe, Arlene H., Mandelbrot, Didier
• Application Number:
  US10/293,809
• Publication Number:
  US 20030232323A1
• Time in Patent Office: Days
• US Class Current: 435/4
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: G01N 2333/70532 B7 molecules, e.g. CD80, CD86
• CPC Class Codes: G01N 2500/02 Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
• CPC Class Codes: G01N 33/505 involving T-cells
• CPC Class Codes: G01N 33/6854 Immunoglobulins
• CPC Class Codes: G01N 33/6872 Intracellular protein regulatory factors and their receptors, e.g. including ion channels

Abstract

Disclosed are methods for identifying an agent that modulates an immune response. One such method comprises screening for agents which inhibit the interaction between a PD-1 ligand and a PD-1 polypeptide, and determining whether the agents inhibit the interaction between a PD-1 ligand and a B7 polypeptide, to identify an agent that inhibits PD-1 ligand and PD-1 polypeptide interaction, while not inhibiting the interaction between a PD-1 ligand and a B7 polypeptide, as an agent that modulates an immune response. Another such method comprises screening for agents which inhibit the interaction between a PD-1 ligand and a B7 polypeptide, and determining whether the agents inhibit the interaction between a PD-1 ligand and a PD-1 polypeptide, to identify an agent that inhibits the PD-1 ligand and B7 polypeptide interaction, which does not inhibit the interaction between a PD-1 ligand and a PD-1 polypeptide, as an agent that modulates the immune response. Further disclosed is a method for inhibiting the interaction between a B7 polypeptide and a PD-1 ligand, the method comprising contacting an immune cell bearing a PD-1 ligand, or an immune cell bearing a B7 polypeptide, with an agent that inhibits the interaction between the PD-1 ligand and the B7 polypeptide. Such agents may be an anti-PD-1 ligand antibody or a small molecule. Also disclosed is a method for modulating an immune response. The method comprises contacting an immune cell bearing the PD-1 ligand, or an immune cell bearing the PD-1 polypeptide, with an agent that inhibits interactions between the PD-1 ligand and the PD-1 polypeptide, without inhibiting interactions between the PD-1 ligand and a B7 polypeptide, to thereby modulate an immune response. The agent may be an anti-PD-1 ligand antibody or a small molecule.

Claims

1. A method for identifying an agent that modulates an immune response, comprising:

a) identifying agents which inhibit the interaction between a PD-1 ligand and a PD-1 polypeptide, from test agents; and

b) determining whether the agents identified in step a) inhibit the interaction between a PD-1 ligand and a B7 polypeptide;

wherein an agent of step b) which does not inhibit the interaction between a PD-1 ligand and a B7 polypeptide, is identified as an agent that modulates an immune response.

2. A method for identifying an agent that modulates an immune response, comprising:

a) identifying agents which inhibit the interaction between a PD-1 ligand and a B7 polypeptide, from test agents; and

b) determining whether the agents identified in step a) inhibit the interaction between a PD-1 ligand and a PD-1 polypeptide;

wherein an agent of step b) which does not inhibit the interaction between a PD-1 ligand and a PD-1 polypeptide, is identified as an agent that modulates an immune response.

3. A method for inhibiting the interaction between a B7 polypeptide and a PD-1 ligand, comprising:

a) contacting an immune cell bearing a PD-1 ligand;

or

b) contacting an immune cell bearing a B7 polypeptide;

with an agent that inhibits the interaction between the PD-1 ligand and the B7 polypeptide.

4. The method of claim 3, wherein the agent is an anti-PD-1 ligand antibody.

5. The method of claim 3, wherein the agent is a small molecule.

6. The method of claim 3, wherein the PD-1 ligand is PD-L1.

7. The method of claim 3, wherein the PD-1 ligand is PD-L2.

8. The method of claim 3, wherein the B7 polypeptide is B7-1.

9. A method for modulating an immune response, comprising:

a) contacting an immune cell bearing the PD-1 ligand;

or

b) contacting an immune cell bearing the PD-1 polypeptide;

with an agent that inhibits interactions between the PD-1 ligand and the PD-1 polypeptide, without inhibiting interactions between the PD-1 ligand and a B7 polypeptide, to thereby modulate an immune response.

10. The method of claim 9, wherein the agent is an anti-PD-1 ligand antibody.

11. The method of claim 9, wherein the agent is a small molecule.

12. The method of claim 9, wherein the PD-1 ligand is PD-L1.

13. The method of claim 9, wherein the PD-1 ligand is PD-L2.

14. The method of claim 9, wherein the B7 polypeptide is B7-1.