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 recombinant Listeria strain expressing a folate hydrolase 1 (FOLH1) peptide, wherein either (a) the sequence of said FOLH1 peptide is a sequence selected from the group consisting of SEQ ID No: 41, 43, 44, and 45; or (b) said FOLH1 peptide is an immunogenic fragment of a larger FOLH1 peptide, wherein the sequence of said larger FOLH1 peptide is selected from the group consisting of SEQ ID No: 41, 43, 44, and 45.
2 . The recombinant Listeria strain of claim 1 , wherein said FOLH1 peptide is in the form of a fusion peptide, wherein said fusion peptide further comprises a non-FOLH1 peptide, wherein said non-FOLH1 peptide enhances the immunogenicity of said fragment.
3 . The recombinant Listeria strain of claim 1 , wherein said non-FOLH1 peptide is selected from the group consisting of a listeriolysin (LLO) peptide, an ActA peptide, and a PEST-like sequence peptide.
4 . The recombinant Listeria strain of claim 1 , wherein said FOLH1 peptide does not contain an FOLH1 signal sequence.
5 . An immunogenic composition comprising the recombinant Listeria strain of claim 1 and an adjuvant.
6 . The recombinant Listeria strain of claim 1 , wherein said recombinant Listeria strain is a recombinant Listeria monocytogenes strain.
7 . The recombinant Listeria strain of claim 1 , wherein said recombinant Listeria strain has been passaged through an animal host.
8 . The recombinant Listeria strain of claim 1 , wherein said Listeria strain is an auxotrophic Listeria strain.
9 . The recombinant Listeria strain of claim 8 , wherein said auxotrophic Listeria strain is a dal/dat mutant.
10 . The recombinant Listeria strain of claim 9 , wherein said auxotrophic Listeria strain comprises an episomal expression vector comprising a metabolic enzyme that complements the auxotrophy of said auxotrophic Listeria strain.
11 . The recombinant Listeria strain of claim 10 , wherein said auxotrophic Listeria further comprises a deletion in the endogenous actA gene.
12 . The recombinant Listeria strain of claim 10 , wherein said metabolic enzyme is an alanine racemase enzyme.
13 . The recombinant Listeria strain of claim 10 , wherein said metabolic enzyme is a D-amino acid transferase enzyme.
14 . A method of inducing an anti-FOLH1 immune response in a subject, comprising administering to said subject a composition comprising the recombinant Listeria strain of claim 1 , thereby inducing an anti-FOLH1 immune response in a subject.
15 . A method of treating a folate hydrolase 1 (FOLH1)-expressing prostate cancer in a subject, the method comprising the step of administering to said subject a composition comprising the recombinant Listeria strain of claim 1 , whereby said subject mounts an immune response against said FOLH1 protein-expressing prostate cancer, thereby treating an FOLH1 protein-expressing prostate cancer in a subject.
16 . A method of protecting a human subject against a folate hydrolase 1 (FOLH1) protein-expressing prostate cancer, the method comprising the step of administering to said human subject a composition comprising the recombinant Listeria strain of claim 1 , whereby said subject mounts an immune response against said FOLH1 protein, thereby protecting a human subject against an FOLH1 protein-expressing prostate cancer.
17 . A recombinant polypeptide comprising a folate hydrolase 1 (FOLH1) peptide operatively linked to a non-FOLH1 peptide, wherein said non-FOLH1 peptide is selected from the group consisting of a listeriolysin (LLO) peptide, an ActA peptide, and a PEST-like amino acid sequence.
18 . An immunogenic composition comprising the recombinant polypeptide of claim 17 and an adjuvant.
19 . A nucleotide molecule encoding the recombinant polypeptide of claim 17 .
20 . An immunogenic composition comprising the nucleotide molecule of claim 20 and an adjuvant.
21 . A recombinant vector comprising the nucleotide molecule of claim 19 .
22 . A method of inducing an anti-FOLH1 immune response in a subject, comprising administering to said subject an immunogenic composition comprising the recombinant polypeptide of claim 17 , thereby inducing an anti-FOLH1 immune response in a subject.
23 . A method of treating an FOLH1 protein-expressing prostate cancer in a subject, the method comprising the step of administering to said subject an immunogenic composition comprising the recombinant polypeptide of claim 17 , whereby said subject mounts an immune response against said FOLH1 protein-expressing prostate cancer, thereby treating an FOLH1 protein-expressing prostate cancer in a subject.
24 . A method of protecting a human subject against an FOLH1 protein-expressing prostate cancer, the method comprising the step of administering to said human subject an immunogenic composition comprising the recombinant polypeptide of claim 17 , whereby said subject mounts an immune response against said FOLH1 protein, thereby protecting a human subject against an FOLH1 protein-expressing prostate cancer.
25 . A method of inducing an anti-FOLH1 immune response in a subject, comprising administering to said subject an immunogenic composition comprising the nucleotide molecule of claim 19 , thereby inducing an anti-FOLH1 immune response in a subject.
26 . A method of treating an FOLH1 protein-expressing prostate cancer in a subject, the method comprising the step of administering to said subject an immunogenic composition comprising the nucleotide molecule of claim 19 , whereby said subject mounts an immune response against said FOLH1 protein-expressing prostate cancer, thereby treating an FOLH1 protein-expressing prostate cancer in a subject.
27 . A method of protecting a human subject against an FOLH1 protein-expressing prostate cancer, the method comprising the step of administering to said human subject an immunogenic composition comprising the nucleotide molecule of claim 19 , whereby said subject mounts an immune response against said FOLH1 protein, thereby protecting a human subject against an FOLH1 protein-expressing prostate cancer.
28 . A recombinant Listeria strain expressing: a kallikrein-related peptidase 3 (KLK3) peptide, wherein the sequence of the KLK3 peptide comprises a sequence selected from the sequences set forth in SEQ ID NO: 27, 29-32, 34, and 36-39, or a sequence greater than 97% identical thereto, wherein the KLK3 peptide is in the form of a fusion peptide and further comprises a non-KLK3 peptide, wherein the non-KLK3 peptide is selected from an ActA peptide and a PEST-like sequence peptide and wherein the non-KLK3 enhances the immunogenicity of the fusion peptide.
29 . The recombinant Listeria strain of claim 28 , wherein said ActA peptide comprises a sequence selected from the sequences set forth in SEQ ID NO: 1-5, 14, 15 or 61, or a sequence greater than 97% identical thereto.
30 . The recombinant Listeria strain of claim 28 , wherein the KLK3 peptide does not contain a KLK3 signal sequence.
31 . The recombinant Listeria strain of claim 28 , wherein the KLK3 peptide contains a KLK3 signal sequence.
32 . The recombinant Listeria strain of claim 28 , wherein the recombinant Listeria strain is an auxotrophic Listeria or a recombinant Listeria monocytogenes strain.
33 . The recombinant Listeria strain of claim 28 , wherein the auxotrophic Listeria strain is a dal/dat mutant and further comprises a deletion in the endogenous ActA gene.
34 . The recombinant Listeria strain of claim 32 , wherein the auxotrophic Listeria strain comprises an episomal expression vector comprising a metabolic enzyme that complements the auxotrophy of the auxotrophic Listeria strain.
35 . The recombinant Listeria strain of claim 34 , wherein the metabolic enzyme is an alanine racemase enzyme or a D-amino acid transferase enzyme.
36 . The recombinant Listeria strain of claim 28 , wherein the recombinant Listeria strain has been passaged through an animal host.
37 . A recombinant polypeptide comprising a kallikrein-related peptidase 3 (KLK3) peptide operatively linked to a non-KLK3 peptide, wherein the sequence of the KLK3 peptide comprises a sequence selected from the sequences set forth in SEQ ID NO: 27, 29-32, 34, and 36-39, or a sequence greater than 97% identical thereto; wherein the non-KLK3 peptide is selected from an ActA peptide, and a PEST-like amino acid sequence.
38 . The recombinant polypeptide of claim 37 , wherein said ActA peptide comprises a sequence selected from the sequences set forth in SEQ ID NO: 1-5, 14, 15 or 61, or a sequence greater than 97% identical thereto.
39 . A nucleotide molecule encoding the recombinant polypeptide of claim 37 .
40 . An immunogenic composition comprising the recombinant Listeria strain of claim 28 .
41 . An immunogenic composition comprising the recombinant polypeptide of claim 37 .
42 . An immunogenic composition comprising the recombinant the nucleotide molecule of claim 39 , and an adjuvant.
43 . A recombinant vector comprising the nucleotide molecule of claim 39 .
44 . A method of producing the recombinant polypeptide of claim 37 , the method comprising the step of chemically conjugating a polypeptide comprising the KLK3 peptide to a polypeptide comprising the non-KLK3 peptide wherein the non-KLK3 peptide is selected from an ActA peptide and a PEST-like sequence peptide.
45 . A method of inducing an anti-KLK3 immune response in a subject, comprising administering to the subject the recombinant Listeria strain of claim 28 .
46 . A method of inducing an anti-KLK3 immune response in a subject the immunogenic composition comprising the recombinant polypeptide of claim 39 .
47 . A method of treating a kallikrein-related peptidase 3 (KLK3)-expressing prostate cancer in a subject, comprising administering to the subject the recombinant Listeria strain of claim 28 .
48 . A method of treating a kallikrein-related peptidase 3 (KLK3)-expressing prostate cancer in a subject, comprising administering the recombinant polypeptide of claim 37 .
49 . A method of protecting a human subject against a kallikrein-related peptidase 3 (KLK3)-expressing prostate cancer, comprising administering to the subject the recombinant Listeria strain of claim 28 .
50 . A method of protecting a human subject against a kallikrein-related peptidase 3 (KLK3)-expressing prostate cancer, comprising administering to the subject the recombinant polypeptide of claim 37 .