Methods of inducing immune responses through the administration of auxtrophic attenuated dal/dat double mutant Listeria strains
View Patent ↗The present invention includes a method of eliciting a T-cell immune response to an antigen in mammal. The method of eliciting a T-cell immune response includes administering mammal an auxotrophic attenuated strain of listeria which expresses the antigen. The auxotrophic attenuated strain of listeria includes a mutation in at least one gene whose protein product is essential for growth of bacteria.
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, wherein said auxotrophic attenuated strain of Listeria comprises a mutation in both the dal and dat genes of Listeria .
2. The method of claim 1 , wherein said antigen is expressed from a vector.
3. The method of claim 1 , wherein said antigen is expressed from the Listeria genome.
4. The method of claim 1 , wherein said auxotrophic attenuated strain of Listeria is administered orally, parenterally, intranasally, intramuscularly, intravascularly, intravenously, intrarectally or intraperitoneally.
5. The method of claim 1 , wherein said cancer cell is a cervical cancer cell.
6. The method of claim 1 , wherein said Listeria is L. monocytogenes .
7. The method of claim 1 , wherein said cancer cell is a melanoma cancer cell, a breast cancer cell, or a leukemia cell.
8. The method of claim 5 , wherein said antigen is HPV E6 of IIPV E7.
9. The method of claim 1 , wherein said antigen is the bcr/abl antigen.
10. The method of claim 1 , wherein said antigen is MΛGE1 or MZ2-E.
11. The method of claim 1 , wherein said antigen is MVC-1 or IIER-2.
12. The method of claim 1 , wherein said antigen is expressed as a fusion protein with lysteriolysin O (LLO) or phosphatidylinositol-specific phospholipase (PI-PLC).
13. The method of claim 1 , wherein said antigen is expressed from a Listeria hly, p60,actΛ, plcA, mpl, plcB, or in1A gene promoter.