Modulators of the function of the core domain of annexins, and uses thereof in autoimmune and/or cancer therapy

1 . A method for identifying a compound that specifically interferes with an extracellular binding interaction between an annexin core domain and a cell surface receptor selected from the group consisting of a Dectin-1 receptor and lipoprotein receptor-related protein-1 (LRP-1), said method comprising:

a) contacting the annexin core domain and said receptor with a compound that interferes with the extracellular binding interaction of said annexin core domain with said receptor, and

b) identifying a specific interference of said extracellular binding interaction between said annexin core domain and said receptor in the presence of said compound, as compared to said extracellular binding interaction in the absence of said compound, as detected by using a method selected from rtPCR, flow cytometry, ELISA, ELISpot, quartz crystal microbalance, immunoprecipitation and measuring an induction or reduction of translocation of said annexin core domain to an outer cell membrane and/or apoptosis in a cell expressing the annexin core domain,

wherein said annexin core domain is selected from the group consisting of an annexin 1 core domain, an annexin 5 core domain, and an annexin 13 core domain.

2 . The method according to claim 1 , wherein said receptor is Dectin-1.

3 . The method according to claim 1 , wherein said interference comprises a decrease or an increase in an activity selected from the group consisting of (a) expression of said annexin, (b) binding of said annexin to said receptor, (c) annexin-mediated immunosuppression, and (d) phagocytosis of apoptotic cells.

4 . The method according to claim 1 , wherein said compound is selected from the group consisting of a peptide, a small molecule, an antisense oligonucleotide, an siRNA, an mRNA, and an antibody, and

wherein said compound specifically interferes with binding of the annexin core domain to said receptor.

5 . The method according to claim 1 , wherein said annexin core domain is an annexin 1 core domain.

6 . The method according to claim 5 , wherein said annexin 1 core domain comprises an amino acid sequence according to SEQ ID NO. 1 or SEQ ID NO. 6.

7 . The method according to claim 1 , wherein said annexin core domain is an annexin 5 core domain.

8 . The method according to claim 7 , wherein said annexin 5 core domain comprises an amino acid sequence according to SEQ ID NO. 2 or SEQ ID NO. 7.

9 . The method according to claim 1 , wherein said annexin core domain is an annexin 13 core domain.

10 . The method according to claim 9 , wherein said annexin 13 core domain comprises an amino acid sequence according to SEQ ID NO. 3 or SEQ ID NO. 8.

11 . A method for identifying a compound that specifically interferes with a binding interaction between an annexin core domain on a cell recombinantly expressing the annexin core domain and a receptor, said method comprising:

a) contacting the cell recombinantly expressing the annexin core domain, and the receptor with a compound that specifically interferes with the binding interaction between said annexin core domain and said receptor, and

(b) detecting a specific interference of the binding interaction between said annexin core domain and said receptor in the presence of said compound as compared to said binding interaction in the absence of said compound as detected by using a method selected from rtPCR, flow cytometry, ELISA, ELISpot, quartz crystal microbalance, immunoprecipitation and measuring an induction or reduction of translocation of said annexin core domain to an outer cell membrane of said cell and/or apoptosis in said cell,

wherein said compound is identified by the detection of the specific interference of said binding interaction,

wherein said annexin core domain is selected from the group consisting of an annexin 1 core domain, an annexin 5 core domain, and an annexin 13 core domain, and,

wherein said receptor is selected from the group consisting of Dectin-1 receptor and LRP-1.

12 . The method according to claim 11 , wherein said receptor is Dectin-1.

13 . The method according to claim 11 , wherein said annexin core domain is an annexin 1 core domain.

14 . The method according to claim 13 , wherein said annexin 1 core domain comprises an amino acid sequence according to SEQ ID NO. 1 or SEQ ID NO. 6.

15 . The method according to claim 11 , wherein said annexin core domain is an annexin 5 core domain.

16 . The method according to claim 15 , wherein said annexin 5 core domain comprises an amino acid sequence according to SEQ ID NO. 2 or SEQ ID NO. 7.

17 . The method according to claim 11 , wherein said annexin core domain is an annexin 13 core domain.

18 . The method according to claim 17 , wherein said annexin 13 core domain comprises an amino acid sequence according to SEQ ID NO. 3 or SEQ ID NO. 8.

19 . The method according to claim 11 , wherein said interference comprises a decrease or an increase in an activity selected from the group consisting of (a) expression of said annexin, (b) binding of said annexin to said receptor, (c) annexin-mediated immunosuppression, and (d) phagocytosis of apoptotic cells.

20 . The method according to claim 11 , wherein said compound is selected from the group consisting of a peptide, a small molecule, an antisense oligonucleotide, an srRNA, an mRNA, and an antibody, and

wherein said compound specifically interferes with binding of the annexin core domain to said receptor.

21 . The method according to claim 11 ,

wherein said cell is selected from the group consisting of a dendritic cell, a macrophage, a cancer cell, an apoptotic cell, an S2 cell, a Mono Mac cell, and a recombinant host cell.

22 . The method according to claim 11 , wherein said cell further expresses said receptor on the cell surface.