Suppressor cell function inhibition following
This invention provides methods and compositions for using a live attenuated Listeria for inhibiting cell-mediated suppression of anti-disease infiltrating T lymphocytes in a subject having the disease.
1. A method of reducing suppression of activated T cells by suppressor cells in an antigen non-specific manner in a subject having asthma or in a disease site within the subject, the method comprising the step of administering to the subject a composition comprising a live attenuated Listeria vaccine strain, wherein said Listeria vaccine strain comprises a recombinant nucleic acid comprising an open reading frame encoding an endogenous Proline, Glutamic acid, Serine, and Threonine (PEST)-containing polypeptide, wherein the PEST-containing polypeptide is not fused to a heterologous antigen, and wherein administration of said Listeria strain reduces the suppression of said activated T cell in said subject or in said disease site within the subject.
2. The method of claim 1 , wherein said activated T cells are CD8+ T cells or CD4+ T cells.
3. The method of claim 1 , wherein said suppressor cells are T-regulatory cells (Treg).
4. The method of claim 1 , wherein said subject is human.
5. The method of claim 1 , wherein said suppressor cells suppress an anti-tumor or cancer T cell response, or an anti-disease T cell response in said subject.
6. The method of claim 1 , wherein said recombinant nucleic acid further comprises an additional open reading frame encoding a metabolic enzyme, wherein said metabolic enzyme complements an endogenous gene that is lacking in the chromosome of said attenuated Listeria strain.
7. The method of claim 6 , wherein said metabolic enzyme encoded by said additional open reading frame is an alanine racemase enzyme or a D-amino acid transferase enzyme.
8. The method of claim 6 , wherein said attenuated Listeria further comprises a mutation or a deletion of a genomic actA gene, a plcA gene, prfA gene or a plcB gene.
9. The method of claim 1 , wherein said recombinant nucleic acid is integrated into the Listeria genome.
10. The method of claim 1 , wherein said recombinant nucleic acid is in a plasmid that is stably maintained in said recombinant Listeria vaccine strain in the absence of antibiotic selection.
11. The method of claim 1 , wherein said PEST-containing polypeptide is an N-terminal truncated Listeriolysin O (LLO) polypeptide, an N-terminal ActA polypeptide, or PEST-peptide.
12. The method of claim 1 , wherein said suppressor cells are myeloid-derived suppressor cells (MDSC).
13. The method of claim 1 , wherein said suppression of activated T cells comprises suppression of T-cell replication of the activated T-cells.
14. The method of claim 1 , wherein said administrating is in combination with other therapeutic modalities useful for enhancing an immune response.