HLA-E BINDING

• US 20080274475A1
• Filed: 04/25/2008
• Published: 11/06/2008
• Est. Priority Date: 12/04/1997
• Status: Abandoned Application

• Current Assignee: Isis Innovation Limited
• Original Assignee: Isis Innovation Limited
• Inventors: O'Callaghan, Christopher A., Ogg, Graham S., Braud, Veronique M., McMichael, Andrew J., Allan, David S.J.
• Application Number:
  US12/109,990
• Publication Number:
  US 20080274475A1
• Time in Patent Office: Days
• US Class Current: 435/7.1
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 16/2851 against the lectin superfamily, e.g. CD23, CD72
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: G01N 2333/70539 MHC-molecules, e.g. HLA-molecules
• CPC Class Codes: G01N 2333/7056 Selectin superfamily, e.g. LAM-1, GlyCAM, ELAM-1, PADGEM
• CPC Class Codes: G01N 33/56977 HLA or MHC typing

Abstract

The invention relates to a method of testing a compound for biological activity, which method comprises providing cells expressing one of the CD94/NKG2 family of receptors, contacting the cells with recombinant HLA-E under binding conditions in the presence of the test compound, and determining whether the presence of the compound affects the binding of HLA-E to the cells. The HLA-E property of binding to CD94/NKG2 receptors on NK cells and a subset of CD8+ T cells is useful for targeting CD94/NKG2+ cells for a variety of purposes such as identification, isolation, killing or inactivation.

Claims

1. A method of preventing HLA-E-mediated inhibition of NK cell activity, comprising:

(a) selecting a compound that interferes with HLA-E-binding to an inhibitory CD94/NKG2 receptor; and

(b) contacting an NK or T cell expressing an inhibitory CD94/NKG2 receptor with the compound.

2. The method of claim 1, wherein the inhibitory CD94/NKG2-receptor is NKG2A.

3. The method of claim 1, wherein the compound is an antibody.

4. The method of claim 3, wherein the antibody is an anti-CD94 antibody.

5. The method of claim 3, wherein the antibody is an anti-NKG2A antibody.

6. The method of claim 3, wherein the antibody is an anti-HLA-E antibody.

7. The method of claim 1, wherein the compound is a multimer of HLA-E comprising two or more HLA-E molecules.

8. The method of claim 7, wherein the multimer has an enhanced binding capability compared to non-multimeric HLA-E.

9. The method of claim 7, wherein the multimer comprises recombinant soluble HLA-E molecules.

10. The method of claim 9, wherein the recombinant soluble HLA-E molecules are attached via a linker molecule.