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 inhibiting prostate cancer metastasis in a subject, comprising:
administering to the 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 the non-KLK3 peptide is a N-terminal non-hemolytic listeriolysin (LLO) peptide, the fusion peptide consisting of the sequence of SEQ ID NO: 54 or a sequence at least 99% homologous (throughout the length of the peptide), wherein the metastasis is inhibited.
2. The method of claim 1 , wherein the recombinant Listeria strain is an auxotrophic Listeria.
3. The method of claim 2 , wherein the auxotrophic Listeria strain is a dal/dat mutant comprising a deletion in the endogenous ActA gene.
4. The method of claim 2 , wherein the auxotrophic Listeria strain comprises an episomal expression vector encoding a metabolic enzyme that complements the auxotrophy of the auxotrophic Listeria strain.
5. The method of claim 4 , wherein the metabolic enzyme is an alanine racemase enzyme.
6. The method of claim 4 , wherein the metabolic enzyme is a D-amino acid transferase enzyme.
7. The method of claim 1 , wherein the recombinant Listeria is a recombinant Listeria monocytogenes strain.
8. The method of claim 1 , wherein the inhibiting prostate cancer metastasis comprises metastasis-free prostate cancer progression.
9. The method of claim 1 , wherein the inhibiting prostate cancer metastasis comprises a reduced rate of growth or reduced number of prostate cancer metastases.
10. A method of treating prostate cancer metastasis in a subject, comprising:
administering to the 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 the non-KLK3 peptide is a N-terminal non-hemolytic listeriolysin (LLO) peptide, the fusion peptide consisting of the sequence of SEQ ID NO: 54 or a sequence at least 99% homologous (throughout the length of the peptide), wherein the subject has metastatic prostate cancer.
11. The method of claim 10 , wherein the recombinant Listeria strain is an auxotrophic Listeria.
12. The method of claim 10 , wherein the auxotrophic Listeria strain is a dal/dat mutant comprising a deletion in the endogenous ActA gene.
13. The method of claim 10 , wherein the auxotrophic Listeria strain comprises an episomal expression vector encoding a metabolic enzyme that complements the auxotrophy of the auxotrophic Listeria strain.
14. The method of claim 13 , wherein the metabolic enzyme is an alanine racemase enzyme.
15. The method of claim 13 , wherein the metabolic enzyme is a D-amino acid transferase enzyme.
16. The method of claim 10 , wherein the recombinant Listeria is a recombinant Listeria monocytogenes strain.