Recombinant cancer therapeutic cytokine

Abstract

Recombinant therapeutic cytokines (“therakines”) for the treatment of cancer are provided. The recombinant therakines include a truncated region of MDA-7/TL-24 (“M4”) not normally found in nature that has anti-cancer activity and a secretory signal which causes secretion of the therakine from plasmid/virus transduced normal and cancer cells and interaction of the therakine to MDA-7/IL-24 receptors on adjacent, neighboring and distant cancer cells. Therakine interaction results in bystander killing of the target cancer cell as well as adjacent, neighboring and distant cancer cells.

1 - 5 . (canceled) 
     
     
         6 . A nucleic acid sequence encoding a recombinant cytokine comprising:
 i) a fragment of MDA-7/IL-24 that has antitumor activity and interacts with MDA-7/IL-24 receptors on the surface of cancer cells; and   ii) a heterologous secretory leader sequence.   
     
     
         7 . The nucleic acid sequence of  claim 6 , wherein said fragment of MDA-7/IL-24 comprises SEQ ID NO: 1. 
     
     
         8 . (canceled) 
     
     
         9 . The nucleic acid sequence of  claim 6 , wherein said heterologous secretory leader sequence comprises SEQ ID NO: 3. 
     
     
         10 . The nucleic acid sequence of  claim 6 , wherein the nucleic acid sequence comprises SEQ ID NO: 6. 
     
     
         11 . A recombinant vector comprising the nucleic acid of  claim 6 , wherein said nucleic acid sequence is operably linked to a promoter. 
     
     
         12 .- 15 . (canceled) 
     
     
         16 . The recombinant vector of  claim 11 , wherein said promoter is a cancer specific or cancer selective promoter. 
     
     
         17 . The recombinant vector of  claim 11 , wherein said recombinant vector is a viral vector. 
     
     
         18 .- 19 . (canceled) 
     
     
         20 . The recombinant vector of  claim 11 , wherein the promoter is selected from the group consisting of: a truncated CCN1 promoter, an mda-9/syntenin promoter, a PEG-Prom, an AEG-1-Prom, and a CMV promoter. 
     
     
         21 . A nanoparticle comprising a nucleic acid sequence encoding a recombinant cytokine comprising:
 i) a fragment of MDA-7/IL-24 that has antitumor activity and interacts with MDA-7/IL-24 receptors on the surface of cancer cells; and   ii) a heterologous secretory leader sequence,   wherein:   a) said heterologous secretory leader sequence comprises SEQ ID NO: 3, or   b) said recombinant cytokine comprises SEQ ID NO: 5,   wherein said nucleic acid sequence is operably linked to a promoter.   
     
     
         22 . A method of treating or preventing cancer and/or cancer metastasis in a subject in need thereof, comprising administering to said subject a recombinant cytokine comprising:
 i) a fragment of MDA 7/IL-24 that has antitumor activity and interacts with MDA-7/IL-24 receptors on the surface of cancer cells; and   ii) a heterologous secretory leader sequence.   
     
     
         23 . The method of  claim 22 , wherein said recombinant cytokine comprises SEQ ID NO: 1. 
     
     
         24 . The method of  claim 22 , wherein said recombinant cytokine is administered as a protein. 
     
     
         25 . The method of  claim 22 , wherein said recombinant cytokine is administered by administering a vector comprising a nucleic acid sequence that encodes said recombinant cytokine. 
     
     
         26 . The method of  claim 24 , wherein said protein comprises SEQ ID NO: 1. 
     
     
         27 . The method of  claim 25 , wherein said nucleic acid sequence comprises SEQ ID NO: 2. 
     
     
         28 . The method of  claim 22 , wherein said cancer is selected from the group consisting of osteosarcoma, ovarian carcinoma, breast carcinoma, melanoma, hepatocarcinoma, lung cancer, brain cancer, colorectal cancer, hematopoietic cell cancer, prostate cancer, cervical carcinoma, retinoblastoma, esophageal carcinoma, bladder cancer, neuroblastoma, renal cancer, gastric cancer, and pancreatic cancer.