Chemokine-cytokine fusion proteins and their applications

Abstract

The present invention provides a fusion protein, comprising a chemokine polypeptide, which is a chemokine or a receptor binding domain thereof; and a cytokine polypeptide connected to said chemokine polypeptide, which is an interleukin, a TNF-superfamily cytokine or a receptor-binding domain thereof; wherein the chemokine polypeptide and the cytokine polypeptide have a common target cell, and the fusion protein has an improved chemokine activity as compared to the chemokine polypeptide, and an improved cytokine activity as compared to the cytokine polypeptide.

What is claimed is: 
     
         1 . A fusion protein, comprising:
 a chemokine polypeptide, which is a chemokine or a receptor binding domain thereof; and   a cytokine polypeptide connected to the chemokine polypeptide, which is a interleukin, a TNF-superfamily cytokine or a receptor binding domain thereof;   wherein the chemokine polypeptide and the cytokine polypeptide have a common target cell, and the fusion protein has an improved chemokine activity as compared to the chemokine polypeptide, and an improved cytokine activity as compared to the cytokine polypeptide.   
     
     
         2 . The fusion protein according to  claim 1 , wherein the chemokine polypeptide and the cytokine polypeptide are connected by a peptide linker. 
     
     
         3 . The fusion protein according to  claim 1 , wherein the chemokine is selected from the group consisting of a CXC chemokine, a CC chemokine, a C chemokine and a CX 3 C chemokine. 
     
     
         4 . The fusion protein according to  claim 3 , wherein the chemokine is a CXC chemokine. 
     
     
         5 . The fusion protein according to  claim 4 , wherein the chemokine is stromal cell-derived factor or IL-8. 
     
     
         6 . The fusion protein according to  claim 1 , wherein the chemokine polypeptide has an amino acid sequence selected from the following: SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18 and a homolog thereof and an analog thereof. 
     
     
         7 . The fusion protein according to  claim 1 , wherein the cytokine polypeptide is IL-2, CD40 ligand or a receptor binding domain thereof. 
     
     
         8 . The fusion protein according to  claim 1 , wherein the cytokine polypeptide has an amino acid sequence selected from the following: SEQ ID NO: 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 and a homolog thereof and an analog thereof. 
     
     
         9 . The fusion protein according to  claim 1 , which has an amino acid sequence selected from the following: SEQ ID NO: 40, 42, 44, 46 and 48. 
     
     
         10 . An isolated nucleic acid molecule encoding a fusion protein according to  claim 1 . 
     
     
         11 . The isolated nucleic acid molecule according to  claim 10 , which comprises a nucleotide sequence encoding a chemokine polypeptide, selected from the following: SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, and a homolog thereof and an analog thereof. 
     
     
         12 . The isolated nucleic acid molecule according to  claim 10 , which comprises a nucleotide sequence encoding a chemokine polypeptide, selected from the following: SEQ ID NO: 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, and a homolog thereof and an analog thereof. 
     
     
         13 . The isolated nucleic acid molecule according to  claim 10 , which has a sequence of one selected from the following: SEQ ID NO: 39, 41, 43, 45 and 47. 
     
     
         14 . An expression vector comprising a nucleic acid molecule according to  claim 10 . 
     
     
         15 . A Host cell comprising a nucleic acid molecule according to  claim 10 . 
     
     
         16 . A Host cell comprising an expression vector of  claim 14 .