SIRP alpha-CD70 FUSION PROTEIN AND METHODS OF USE THEREOF

Abstract

SIRPalpha-CD70 fusion proteins are provided. Accordingly, there is provided a SIRPalpha-CD70 fusion protein comprising a single amino acid linker between the SIRPalpha and the CD70. Also there is provided a SIRPalpha-CD70 fusion protein in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the SIRPalpha-CD70 fusion protein, host-cells expressing the SIRPalpha-CD70 fusion protein and methods of use thereof.

What is claimed is: 
     
         1 . A SIRPα-CD70 fusion protein comprising a single amino acid linker between said SIRPα and said CD70; and/or in a form of at least a homo-trimer. 
     
     
         2 . The SIRPα-CD70 fusion protein of  claim 1 , wherein said at least homo-trimer is at least 140 kD in molecular weight as determined by SDS-PAGE. 
     
     
         3 . The SIRPα-CD70 fusion protein of  claim 1 , wherein the SIRPα-CD70 fusion protein comprises a linker between said SIRPα and said CD70. 
     
     
         4 . The SIRPα-CD70 fusion protein of  claim 3 , wherein the linker is not an Fc domain of an antibody or a fragment thereof. 
     
     
         5 . The SIRPα-CD70 fusion protein of  claim 1 , wherein the linker is glycine. 
     
     
         6 . The SIRPα-CD70 fusion protein of  claim 1 , being soluble. 
     
     
         7 . The SIRPα-CD70 fusion protein of  claim 1 , wherein said SIRPα comprises an extracellular domain of said SIRPα or a functional fragment thereof. 
     
     
         8 . The SIRPα-CD70 fusion protein of  claim 1 , wherein said CD70 comprises an extracellular domain of said CD70 or a functional fragment thereof. 
     
     
         9 . The SIRPα-CD70 fusion protein of  claim 1 , wherein said fusion protein is capable of at least one of:
 (i) binding CD47 and CD27; 
 (ii) activating said CD27 signaling pathway in a cell expressing said CD27; 
 (iii) co-stimulating immune cells expressing said CD27; and/or 
 (iv) enhancing phagocytosis of pathologic cells expressing said CD47 by phagocytes compared to same in the absence of said SIRPα-CD70 fusion protein. 
 
     
     
         10 . The SIRPα-CD70 fusion protein of  claim 1 , wherein said SIRPα amino acid sequence is at least 90% identical to the amino acid sequence as set forth in SEQ ID NO: 2 or 9. 
     
     
         11 . The SIRPα-CD70 of  claim 1 , wherein said CD70 amino acid sequence is at least 90% identical to the amino acid sequence as set forth in SEQ ID NO: 3 or 12. 
     
     
         12 . A host cell comprising the SIRPα-CD70 fusion protein of  claim 1 . 
     
     
         13 . An article of manufacture identified for the treatment of a disease that can benefit from activating immune cells comprising a packaging material packaging a therapeutic agent for treating said disease; and the SIRPα-CD70 fusion protein of  claim 1 .