Methods and compositions for immunotherapy of cancer
View Patent ↗The present invention includes compositions, methods and kits for inducing an immune response to a tumor and for treating cancer with a Listeria vaccine strain expressing an antigen fused to a truncated LLO protein.
1. A method of treating a breast cancer in a human subject, the method comprising administering to said human subject a Listeria vaccine strain, wherein said Listeria vaccine strain comprises a nucleic acid encoding a truncated listeriolysin O (LLO) protein fused to a Her-2/neu protein fragment, wherein said truncated LLO protein comprises the sequence set forth in SEQ ID NO: 10 and does not comprise cysteine 484, wherein said Her-2/neu protein fragment consists of amino acid residues selected from the group consisting of SEQ ID NO: 4 and SEQ ID NO: 5 of said Her-2/neu protein, and wherein at least one cell of said breast cancer expresses a Her-2/neu protein, thereby treating a breast cancer in a human subject.
2. The method of claim 1 , wherein said Listeria vaccine strain is a Listeria monocytogenes vaccine strain.
3. The method of claim 1 , wherein said truncated LLO protein fused to a Her-2/neu protein fragment is expressed from a plasmid.
4. The method of claim 1 , wherein said nucleic acid encoding said truncated LLO protein fused to a Her-2/neu protein fragment is stably integrated into the chromosome of said Listeria vaccine strain.
5. The method of claim 1 , wherein said vaccine strain is administered intravenously.
6. A method of suppressing tumor formation associated with breast cancer in a human subject, the method comprising administering to said human subject a Listeria vaccine strain, wherein said Listeria vaccine strain comprises a nucleic acid encoding a truncated listeriolysin O (LLO) protein fused to a Her-2/neu protein fragment, wherein said truncated LLO protein comprises the sequence set forth in SEQ ID NO: 10 and does not comprise cysteine 484, wherein said Her-2/neu protein fragment consists of amino acid residues selected from the group consisting of SEQ ID NO: 4 and SEQ ID NO: 5 of said Her-2/neu protein, and wherein at least one cell of said breast cancer expresses a Her-2/neu protein, thereby treating a breast cancer in a human subject.
7. The method of claim 6 , wherein said Listeria vaccine strain is a Listeria monocytogenes vaccine strain.
8. The method of claim 6 , wherein said truncated LLO protein fused to a Her-2/neu protein fragment is expressed from a plasmid.
9. The method of claim 6 , wherein said nucleic acid encoding said truncated LLO protein fused to a Her-2/neu protein fragment is stably integrated into the chromosome of said Listeria vaccine strain.
10. The method of claim 6 , wherein said vaccine strain is administered intravenously.
11. A method of inducing an immune response to a breast cancer in a human subject, the method comprising administering to said human subject a Listeria vaccine strain, wherein said Listeria vaccine strain comprises a nucleic acid encoding a truncated listeriolysin O (LLO) protein fused to a Her-2/neu protein fragment, wherein said truncated LLO protein comprises the sequence set forth in SEQ ID NO: 10 and does not comprise cysteine 484, wherein said Her-2/neu protein fragment consists of amino acid residues selected from the group consisting of SEQ ID NO: 4 and SEQ ID NO: 5 of said Her-2/neu protein, and wherein at least one cell of said breast cancer expresses a Her-2/neu protein, thereby treating a breast cancer in a human subject.
12. The method of claim 11 , wherein said Listeria vaccine strain is a Listeria monocytogenes vaccine strain.
13. The method of claim 11 , wherein said truncated LLO protein fused to a Her-2/neu protein fragment is expressed from a plasmid contained in said Listeria vaccine strain.
14. The method of claim 11 , wherein said nucleic acid encoding said truncated LLO protein fused to a Her-2/neu protein fragment is stably integrated into the chromosome of said Listeria vaccine strain.
15. The method of claim 11 , wherein said vaccine strain is administered intraperitoneally.