Compositions and methods comprising KLK3 or FOLH1 antigen
The present invention provides KLK3 peptides, FOLH1 peptides, recombinant polypeptides comprising same, recombinant nucleotide molecules encoding same, recombinant Listeria strains comprising same, and immunogenic and therapeutic methods utilizing same.
1. A method of inducing an anti-KLK3 immune response in a subject, comprising administering to said subject a composition comprising a recombinant Listeria strain encoding a recombinant fusion peptide consisting of a KLK3 peptide operatively linked to a non-KLK3 peptide, wherein said non-KLK3 peptide is a N-terminal non-hemolytic listeriolysin (LLO) peptide, said fusion peptide consisting of the sequence of SEQ ID NO: 54 or a sequence at least 99% homologous (throughout the length of the peptide) thereto, wherein said N-terminal LLO peptide enhances the immunogenicity of the fusion peptide, thereby inducing an anti-KLK3 immune response in a subject.
2. The method of claim 1 , wherein said recombinant Listeria strain is an auxotrophic Listeria.
3. The method of claim 2 , wherein said auxotrophic Listeria strain is a dal/dat mutant.
4. The method of claim 2 , wherein said auxotrophic Listeria further comprises a deletion in the endogenous ActA gene.
5. The method of claim 2 , wherein said auxotrophic Listeria strain further comprises a deletion in the endogenous ActA gene and is a dal/dat mutant.
6. The method of claim 2 , wherein said auxotrophic Listeria strain comprises an episomal expression vector comprising a metabolic enzyme that complements the auxotrophy of said auxotrophic Listeria strain.
7. The method of claim 6 wherein said metabolic enzyme is an alanine racemase enzyme.
8. The method of claim 6 , wherein said metabolic enzyme is a D-amino acid transferase enzyme.
9. The method of claim 1 , wherein said recombinant Listeria is a recombinant Listeria monocytogenes strain.
10. A method of treating a kallikrein-related peptidase 3 (KLK3)-expressing prostate cancer in a subject, the method comprising the step of administering to said subject a composition comprising a recombinant Listeria strain encoding a recombinant fusion peptide consisting of a KLK3 peptide operatively linked to a non-KLK3 peptide, wherein said non-KLK 3 peptide is a N-terminal non-hemolytic listeriolysin (LLO) peptide, said fusion peptide consisting of the sequence of SEQ ID NO: 54 or a sequence at least 99% homologous (throughout the length of the peptide) thereto, wherein said N-terminal LLO peptide enhances the immunogenicity of the fusion peptide, whereby said subject mounts an immune response against said KLK3 protein-expressing prostate cancer, thereby treating a KLK3 protein-expressing prostate cancer in a subject.
11. The method of claim 10 , wherein said recombinant Listeria strain is an auxotrophic Listeria.
12. The method of claim 11 , wherein said auxotrophic Listeria strain is a dal/dat mutant.
13. The method of claim 11 , wherein said auxotrophic Listeria further comprises a deletion in the endogenous ActA gene.
14. The method of claim 11 , wherein said auxotrophic Listeria strain further comprises a deletion in the endogenous ActA gene and is a dal/dat mutant.
15. The method of claim 11 , wherein said auxotrophic Listeria strain comprises an episomal expression vector comprising a metabolic enzyme that complements the auxotrophy of said auxotrophic Listeria strain.
16. The method of claim 15 wherein said metabolic enzyme is an alanine racemase enzyme.
17. The method of claim 15 , wherein said metabolic enzyme is a D-amino acid transferase enzyme.
18. The method of claim 10 , wherein said recombinant Listeria is a recombinant Listeria monocytogenes strain.
19. A method of protecting a human subject against a kallikrein-related peptidase 3 (KLK3) protein-expressing prostate cancer, the method comprising the step of administering to said human subject a composition comprising a recombinant Listeria strain encoding a recombinant fusion peptide consisting of a KLK3 peptide operatively linked to a non-KLK3 peptide, wherein said non-KLK3 peptide is a N-terminal non-hemolytic listeriolysin (LLO) peptide, said fusion peptide consisting of the sequence of SEQ ID NO: 54 or a sequence at least 99% homologous (throughout the length of the peptide) thereto, wherein said N-terminal LLO peptide enhances the immunogenicity of the fusion peptide, whereby said subject mounts an immune response against said KLK3protein, thereby protecting a human subject against a KLK3 protein-expressing prostate cancer.
20. The method of claim 19 , wherein said recombinant Listeria strain is an auxotrophic Listeria.
21. The method of claim 20 , wherein said auxotrophic Listeria strain is a dal/dat mutant.
22. The method of claim 20 , wherein said auxotrophic Listeria further comprises a deletion in the endogenous ActA gene.
23. The method of claim 20 , wherein said auxotrophic Listeria strain further comprises a deletion in the endogenous ActA gene and is a dal/dat mutant.
24. The method of claim 20 , wherein said auxotrophic Listeria strain comprises an episomal expression vector comprising a metabolic enzyme that complements the auxotrophy of said auxotrophic Listeria strain.
25. The method of claim 24 wherein said metabolic enzyme is an alanine racemase enzyme.
26. The method of claim 24 , wherein said metabolic enzyme is a D-amino acid transferase enzyme.
27. The method of claim 19 , wherein said recombinant Listeria is a recombinant Listeria monocytogenes strain.
28. A recombinant fusion peptide comprising a KLK3 peptide operatively linked to a non-KLK3 peptide, wherein said non-KLK3 peptide is a N-terminal non-hemolytic listeriolysin (LLO) peptide, said fusion peptide consisting of the sequence of SEQ ID NO: 54 or a sequence at least 99% homologous (throughout the length of the peptide) thereto.
29. The recombinant fusion peptide of claim 28 , wherein said KLK3peptide does not contain a KLK3 signal sequence.
30. A vaccine comprising the composition of claim 28 and an adjuvant.
31. The vaccine of claim 30 , wherein said adjuvant comprises Montanide ISA 51, GM-CSF, KLH, a cytokine, a growth factor, a cell population, QS21, Freund's incomplete adjuvant, aluminum phosphate, aluminum hydroxide, BCG, alum, an interleukin, an unmethylated CpG oligonucleotide, quill glycosides, monophosphoryl lipid A, a liposomes, a bacterial mitogen, a bacterial toxin, or a chemokine, or any combination thereof.