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 comprising a sequence encoding a recombinant cytokine, the recombinant cytokine comprising:
 i) an amino acid sequence that is at least 90% identical to SEQ ID NO: 1; and   ii) a secretory leader sequence that is at least 90% identical to SEQ ID NO: 3.   
     
     
         7 . The nucleic acid of  claim 6 , wherein said recombinant cytokine comprises SEQ ID NO: 1. 
     
     
         8 . (canceled) 
     
     
         9 . The nucleic acid of  claim 6 , wherein said secretory leader sequence comprises SEQ ID NO: 3. 
     
     
         10 . The nucleic acid of  claim 6 , wherein the nucleic acid comprises SEQ ID NO: 6. 
     
     
         11 . A recombinant vector comprising the nucleic acid of  claim 6 , wherein the sequence encoding the recombinant cytokine is operably linked to a promoter. 
     
     
         12 . The nucleic acid of  claim 6 , wherein the recombinant cytokine comprises SEQ ID NO: 5. 
     
     
         13 .- 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 the nucleic acid of  claim 6 . 
     
     
         22 . A method of treating or preventing cancer and/or cancer metastasis in a subject in need thereof, comprising administering to said subject a nucleic acid of  claim 6 . 
     
     
         23 . The method of  claim 22 , wherein said recombinant cytokine comprises SEQ ID NO: 1. 
     
     
         24 . The method of  claim 22 , wherein said secretory leader sequence comprises SEQ ID NO: 3. 
     
     
         25 . The method of  claim 22 , wherein the nucleic acid is administered by administering a vector comprising the nucleic acid. 
     
     
         26 . The method of  claim 24 , wherein the recombinant cytokine comprises SEQ ID NO: 5. 
     
     
         27 . (canceled) 
     
     
         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. 
     
     
         29 .- 34 . (canceled)