Immunogenic compositions comprising dal/dat double mutant, auxotrophic attenuated strains of Listeria and their methods of use

Abstract

The invention includes auxotrophic attenuated mutants of Listeria and methods of their use as vaccines.

1 . A method of inducing an immune response against a cancer cell in a mammal, the method comprising administering to said mammal an auxotrophic attenuated strain of  Listeria  comprising an antigen expressed by said cancer cell. 
     
     
         2 . The method of  claim 1 , wherein the auxotrophic attenuated strain of  Listeria  comprises a mutation in the dal gene. 
     
     
         3 . The method of  claim 1 , wherein the auxotrophic attenuated strain of  Listeria  comprises a mutation in the dat gene. 
     
     
         4 . The method of  claim 3 , wherein the auxotrophic attenuated strain of  Listeria  further comprises a mutation in the dal gene. 
     
     
         5 . The method of  claim 1 , wherein said antigen is expressed from a vector. 
     
     
         6 . The method of  claim 1 , wherein said antigen is expressed from the  Listeria  genome. 
     
     
         7 . The method of  claim 1 , wherein said auxotrophic attenuated strain of  Listeria  is administered orally, parenterally, intranasally, intramuscularly, intravascularly, intravenously, intrarectally, or intraperitoneally. 
     
     
         8 . The method of  claim 1 , wherein said cancer cell is a cervical cancer cell. 
     
     
         9 . The method of  claim 1 , wherein said cancer cell is a melanoma cancer cell, a breast cancer cell, or a leukemia cell. 
     
     
         10 . The method of  claim 1 , wherein said  Listeria  is  L. monocytogenes.    
     
     
         11 . The method of claim  26 , wherein said antigen is HPV E6, HPV E7, or a combination thereof. 
     
     
         12 . The method of  claim 1 , wherein said antigen is the bcr/abl antigen. 
     
     
         13 . The method of  claim 1 , wherein said antigen is MAGE1, MZ2-E or a combination thereof. 
     
     
         14 . The method of  claim 1 , wherein said antigen is MVC-1, HER-2 or a combination thereof. 
     
     
         15 . The method of  claim 1 , wherein said antigen is expressed as a fusion protein with listeriolysin O (LLO), phosphatidylinositol-specific phospholipase (PI-PLC), or a combination thereof. 
     
     
         16 . The method of  claim 1 , wherein said antigen is expressed from a  Listeria  hly, p60, actA, picA, mpl, plcB, or inlA gene promoter. 
     
     
         17 . The method of  claim 1 , wherein said immune response is a cytotoxic T cell response.