Vectors for the diagnosis and treatment of solid tumors including melanoma

Abstract

The present invention is directed to the isolation and use of super-infective, tumor-specific vectors that are strains of parasites including, but not limited to bacteria, fungi and protists. In certain embodiments the parasites include, but are not limited to, the bacterium Salmonella spp., such as Salmonella typhimurium , the bacterium Mycobacterium avium and the protozoan Leishmania amazonensis . In other embodiments, the present invention is concerned with the isolation of super-infective, tumor-specific, suicide gene-containing strains of parasites for use in treatment of solid tumors.

1 . A method for reducing volume or inhibiting growth of a solid tumor cancer, comprising: administering to a patient having a solid tumor, a tumor specific  Escherichia coli  genetically engineered to express a suicide gene.  
     
     
         2 . The method according to  claim 1  wherein the tumor specific  E. coli  is attenuated.  
     
     
         3 . The method according to  claim 2  wherein the attenuated tumor specific  E. coli  expresses an altered lipid A molecule.  
     
     
         4 . The method according to  claim 2  wherein the attenuated tumor specific  E. coli  induces TFN-α expression in monocytes or macrophages from about 1 to about 75 percent compared to non-attenuated microorganisms.  
     
     
         5 . The method according to  claim 1 , wherein the tumor specific  E. coli  is a single colony clone of an isolated population of  E. coli  microorganisms.  
     
     
         6 . The method accordingly to  claim 1 , wherein the tumor specific microorganism is an enteroinvasive  E. coli  genetically engineered to express a suicide gene.  
     
     
         7 . The method according to  claim 1  wherein the suicide gene is encoded by the open reading frame of the insert of a plasmid selected from the group consisting of pTK-Sec3, pCD-Sec1 and pSP-SAD4-5.  
     
     
         8 . The method according to  claim 1  wherein the tumor specific  E. coli  expresses a suicide gene selected from the group consisting of p450 oxidoreductase, HSV thymidine kinase,  E. coli  cytosine deaminase, carboxypeptidase G2, β-glucuronidase, penicillin-V-amidase, penicillin-G-amidase, β-lactamase, β-glucosidase, nitroreductase and carboxypeptidase A.  
     
     
         9 . The method according to  claim 1  wherein the suicide gene is HSV thymidine kinase or  E. coli  cytosine deaminase.  
     
     
         10 . The method according to  claim 1  wherein the  E. coli  expresses the suicide gene under control of a constitutive promoter, an inducible promoter, or a tumor cell specific promoter.  
     
     
         11 . The method according to  claim 1 , wherein the  E. coli  is an auxotrophic mutant.  
     
     
         12 . The method accordingly to  claim 1 , wherein the tumor specific microorganism is super-infective.  
     
     
         13 . The method according to  claim 1 , wherein the tumor specific microorganism is attenuated and super-infective.