Pd1-cd70 fusion protein and methods of use thereof

Abstract

PD1-CD70 fusion proteins are provided. Accordingly, there is provided a PD1-CD70 fusion protein comprising a single amino acid linker between the PD1 and the CD70. Also there is provided a PD1-CD70 fusion protein, wherein the PD1 amino acid is 123-166 amino acids in length and/or wherein the PD1 amino acid sequence comprises SEQ ID NO: 2 and/or wherein the fusion protein is in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the PD1-CD70 fusion protein, host-cells expressing the PD1-CD70 fusion protein and methods of use thereof.

What is claimed is: 
     
         1 . A PD1-CD70 fusion protein being characterized by a single amino acid linker between said PD1 and said CD70; a PD1 amino acid as set forth in SEQ ID NO 2 or at least 123 amino acids long fragment thereof capable of binding PD-L1; and/or being in a form of a homo-trimer. 
     
     
         2 . The PD1-CD70 fusion protein of  claim 1 , wherein said homo-trimer is at least 140 kD in molecular weight as determined by SDS-PAGE. 
     
     
         3 . The PD1-CD70 fusion protein of  claim 1 , wherein the linker is glycine. 
     
     
         4 . The PD1-CD70 fusion protein of  claim 1 , wherein said fusion protein is capable of at least one of:
 (i) binding PD-L1 and CD27;   (ii) activating said CD27 signaling pathway in a cell expressing said CD27; and/or   (iii) co-stimulating immune cells expressing said CD27.   
     
     
         5 . The PD1-CD70 fusion protein of  claim 1 , being soluble. 
     
     
         6 . A polynucleotide encoding the PD1-CD70 fusion protein of  claim 1 . 
     
     
         7 . A nucleic acid construct comprising the polynucleotide of  claim 6 , and a regulatory element for directing expression of said polynucleotide in a host cell. 
     
     
         8 . A host cell comprising the PD1-CD70 fusion protein of  claim 1 . 
     
     
         9 . A method of producing a PD1-CD70 fusion protein, the method comprising expressing in a host cell the polynucleotide of  claim 6 . 
     
     
         10 . The method of  claim 9 , comprising isolating the fusion protein. 
     
     
         11 . A method of treating a disease that can benefit from activating immune cells comprising administering to a subject in need thereof the PD1-CD70 fusion protein of  claim 1 . 
     
     
         12 . The method of  claim 11 , wherein said disease comprises a hyper-proliferative disease, a disease associated with immune suppression or medication induced immunosuppression, or an infection. 
     
     
         13 . The method of  claim 12 , wherein said hyper-proliferative disease comprises cancer. 
     
     
         14 . 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 PD1-CD70 fusion protein of  claim 1 , a polynucleotide encoding same, a nucleic acid construct encoding same or a host cell expressing same. 
     
     
         15 . The article of manufacture of  claim 14 , wherein said disease comprises a hyper-proliferative disease, a disease associated with immune suppression or medication induced immunosuppression, or an infection. 
     
     
         16 . A method of treating cancer comprising administering to a subject in need thereof an anti-cancer agent; and the PD1-CD70 fusion protein of  claim 1 , a polynucleotide encoding same, a nucleic acid construct encoding same or a host cell expressing same. 
     
     
         17 . The method of  claim 16 , wherein said anti-cancer agent comprises an antibody. 
     
     
         18 . A method of activating immune cells, the method comprising in-vitro activating immune cells in the presence of the PD1-CD70 fusion protein of  claim 1 , a polynucleotide encoding same, a nucleic acid construct encoding same or a host cell expressing same. 
     
     
         19 . The method of  claim 18 , wherein said activating is in the presence of cells expressing PD-L1 or exogenous PD-L1. 
     
     
         20 . The method of  claim 18 , comprising adoptively transferring said immune cells following said activating to a subject in need thereof.