Light emitting microorganisms and cells for diagnosis and therapy of tumors

Abstract

Described are diagnostic and pharmaceutical compositions comprising a microorganism or cell containing a DNA sequence encoding a detectable protein or a protein capable of inducing a detectable signal, e.g. a luminescent or fluorescent protein. Moreover, the use of said microorganism or cell for tumor-targeting or tumor-imaging is described. For therapeutic uses, said microorganism or cell additionally contain an expressible DNA sequence encoding a protein suitable for tumor therapy, e.g. a cytotoxic or cytostatic protein.

1 . A diagnostic or pharmaceutical composition comprising a microorganism or cell containing a DNA sequence encoding a detectable protein or a protein capable of inducing a detectable signal.  
     
     
         2 . The diagnostic or pharmaceutical composition of  claim 1 , wherein the protein capable of inducing a detectable signal is a luminescent and/or fluorescent protein.  
     
     
         3 . The diagnostic or pharmaceutical composition of  claim 1 , wherein the protein capable of inducing a detectable signal is a protein inducing a signal detectable by magnetic resonance imaging (MRI) or capable of binding a contrasting agent, chromophore or a ligand required for visualization of tissues.  
     
     
         4 . The diagnostic or pharmaceutical composition of any one of  claims 1  to  3 , wherein the migroorganism is a bacterium or a virus.  
     
     
         5 . The diagnostic or pharmaceutical composition of  claim 4 , wherein the virus is Vaccinia virus.  
     
     
         6 . The diagnostic or pharmaceutical composition of  claim 4 , wherein the bacterium is attenuated  Salmonella thyphimurium,  attenuated  Vibrio cholerae,  attenuated  Listeria monocytogenes  or  E. coli.    
     
     
         7 . The diagnostic or pharmaceutical composition of  claim 1 , wherein the cell is a mammalian cell.  
     
     
         8 . The diagnostic or pharmaceutical composition of any one of  claims 1  to  7 , wherein the luminescent or fluorescent protein is luciferase, RFP or GFP.  
     
     
         9 . The diagnostic or pharmaceutical composition of any one of  claims 1  to  8 , wherein the microorganism or cell additionally contains a gene encoding a substrate for a luciferase.  
     
     
         10 . Use of the microorganism or cell as defined in any one of  claims 1  to  9  for the preparation of a diagnostic composition for tumor-imaging or monitoring a therapeutic tumor treatment.  
     
     
         11 . Use according to  claim 10 , wherein tumor-imaging or monitoring is carried out by MRI.  
     
     
         12 . A pharmaceutical composition containing a microorganism or cell as defined in any one of  claims 1  to  9 , wherein said microorganism or cell furthermore contains one or more expressible DNA sequences encoding (a) protein(s) suitable for tumor therapy and/or elimination of metastatic tumors.  
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein the protein suitable for tumor therapy and/or elimination of metastatic tumors is endostatin or recombinant chimeric toxin PE37/transforming growth factor alpha (TGF-alpha).  
     
     
         14 . The pharmaceutical composition according to  claim 12  or  13 , wherein the expressible DNA sequences are on a BAC, MAC, cyber cell or cyber virus.  
     
     
         15 . Use of the microorganism or cell as defined in any one of  claims 12  to  14  for the preparation of a pharmaceutical composition for tumor therapy and/or elimination of a metastatic tumor.  
     
     
         16 . Use according to  claim 15 , wherein the tumor is a bladder tumor, breast tumor, prostate tumor, glioma tumor, liver tumor, skin tumor, adenocarcinoma, ovarial carcinoma or pancreatic carcinoma.