Humanised Baculovirus

Abstract

A genetically engineered baculovirus which is engineered to target therapeutic agents to cells, typically cancer cells, for example prostate cancer cells.

1 . A baculovirus wherein the baculovirus genome has been modified to comprise a first nucleic acid molecule which encodes a therapeutic agent and a second nucleic acid molecule that encodes a baculovirus capsid polypeptide fused to a neurotensin peptide which binds the baculovirus to the cell surface of at least one cell type. 
     
     
         2 . A baculovirus according to  claim 1 , wherein said genome is adapted for eukaryotic gene expression of said nucleic acid molecules. 
     
     
         3 . A baculovirus according to  claim 1 , wherein the expression of said nucleic acid molecule encoding a therapeutic agent is controlled by a cancer specific promoter. 
     
     
         4 . A baculovirus according to  claim 3 , wherein said cancer specific promoter is a prostate cancer cell specific promoter. 
     
     
         5 . A baculovirus according to  claim 1 , wherein said therapeutic agent is a polypeptide. 
     
     
         6 . A baculovirus according to  claim 5 , wherein said polypeptide is a tumour suppressor polypeptide selected from the group consisting of: p53, retinoblastoma, APC polypeptide, DPC-4 polypeptide, BRCA 1 polypeptide, BRCA 2 polypeptide, WT 1 polypeptide, MMAC 1 polypeptide, familial polyposis coli polypeptide. 
     
     
         7 . A baculovirus according to  claim 5 , wherein said polypeptide is an antigenic polypeptide. 
     
     
         8 . A baculovirus according to  claim 7 , wherein said antigenic polypeptide is a prostate tumour rejection antigen. 
     
     
         9 . A baculovirus according to  claim 5 , wherein said polypeptide is a cytotoxic polypeptide. 
     
     
         10 . A baculovirus according to  claim 9 , wherein said cytotoxic agent is selected from the group consisting of pseudomonas exotoxin, ricin toxin, and diptheria toxin. 
     
     
         11 . A baculovirus according to  claim 5 , wherein said polypeptide is a polypeptide which induces cell-cycle arrest. 
     
     
         12 . A baculovirus according to  claim 11 , wherein said polypeptide is selected from the group consisting of p21, p16, p15, p18, p19, and PTEN. 
     
     
         13 . A baculovirus according to  claim 5 , wherein said therapeutic polypeptide is a pharmaceutically active polypeptide. 
     
     
         14 . A baculovirus according to  claim 13 , wherein said polypeptide is a cytokine. 
     
     
         15 . A baculovirus according to  claim 14 , wherein said cytokine is selected from the group consisting of growth hormone, leptin, erythropoietin, prolactin, IL2, IL3, IL4, IL5, IL6, IL7, IL9, IL10, IL11, p53 subunit of IL12, IL13, IL15, G-CSF, GM-CSF, CNTF, CT-1, LIF, oncostatin, and IFNα. 
     
     
         16 . A baculovirus according to  claim 5 , wherein said polypeptide is an antibody or active binding fragment thereof. 
     
     
         17 . A baculovirus according to  claim 16 , wherein said fragment is a Fab fragment. 
     
     
         18 . A baculovirus according to  claim 5 , wherein said polypeptide is a polypeptide which induces apoptosis. 
     
     
         19 . A baculovirus according to  claim 18 , wherein said polypeptide is selected from the group consisting of p53, adenovirus E3.11.6K, adenovirus E4, adenovirus f4, caspase, Fas ligand, C-Cam 1, ODC, OAZ, spermidine/spermine N1 acetyltransferase, ZNF145, PTEN phosphatase, androgen receptor, and Bcl 2. 
     
     
         20 . A baculovirus according to  claim 5 , wherein said polypeptide is a pro-drug activating polypeptide. 
     
     
         21 . A baculovirus according to  claim 20 , wherein said polypeptide is selected from the group consisting of cytosine deaminase, thymidine kinase, nitroreductase RdxA, cytochrome p450 CYP1A2, cytochrome p450 CYP2 μl, and cytochrome p450 CYP3A4. 
     
     
         22 . A baculovirus according to  claim 21 , wherein said polypeptide has anti-angiogenic activity. 
     
     
         23 . A baculovirus according to  claim 22 , wherein said polypeptide is selected from the group consisting of: angiostatin, Tie2, and endostatin. 
     
     
         24 . A baculovirus according to  claim 1 , wherein said therapeutic agent is an antisense nucleic acid molecule. 
     
     
         25 . A baculovirus according to  claim 25 , wherein said antisense nucleic acid molecule binds a nucleic acid molecule encoding a cell-cycle regulatory gene. 
     
     
         26 . A baculovirus according to  claim 25 , wherein said cell-cycle regulatory gene is selected from the group consisting of: p21, p16, p15, p18, p19, and PTEN. 
     
     
         27 . A baculovirus according to  claim 24 , wherein said antisense nucleic acid molecule binds a nucleic acid molecule encoding an apoptosis inhibitor. 
     
     
         28 . A baculovirus according to  claim 27 , wherein said apoptosis inhibitor is caveolin. 
     
     
         29 . A baculovirus according to  claim 1 , wherein said therapeutic agent is a double stranded RNA molecule. 
     
     
         30 . A baculovirus according to  claim 1 , wherein said therapeutic agent is a ribozyme. 
     
     
         31 . A baculovirus according to  claim 1 , wherein said capsid polypeptide is gp64. 
     
     
         32 . A baculovirus according to  claim 1 , wherein said cell type is a prostate cancer cell. 
     
     
         33 . A pharmaceutical composition comprising the baculovirus according to  claim 1 , and at least one pharmaceutically acceptable carrier or adjuvant. 
     
     
         34 . A method of treating cancer in a subject in need thereof, said method comprising administering to said subject a therapeutically effective amount of the baculovirus according to  claim 1 . 
     
     
         35 . A method according to  claim 34 , wherein said cancer is prostate cancer. 
     
     
         36 . A baculovirus according to  claim 1 , wherein said neurotensin peptide consists of the amino acid sequence SEQ ID NO: 4.