Provided herein are recombinant Listeria strains expressing a tumor-specific antigenic polypeptide and, optionally, an angiogenic polypeptide wherein a nucleic acid molecule encoding at least one of the polypeptides is operably integrated into the Listeria genome in an open reading frame with a nucl
Provided herein are recombinant Listeria strains expressing a tumor-specific antigenic polypeptide and, optionally, an angiogenic polypeptide wherein a nucleic acid molecule encoding at least one of the polypeptides is operably integrated into the Listeria genome in an open reading frame with a nucleic acid sequence encoding a PEST-containing polypeptide, methods of preparing same, and methods of inducing an immune response, and treating, inhibiting, or suppressing cancer or tumors comprising administering same.
대표청구항▼
1. A recombinant Listeria strain comprising a nucleic acid molecule encoding a fusion polypeptide, wherein said fusion polypeptide comprises a heterologous antigen fused to an N-terminal LLO, wherein said recombinant Listeria is an attenuated Listeria comprising a mutation in the dal/dat genes, wher
1. A recombinant Listeria strain comprising a nucleic acid molecule encoding a fusion polypeptide, wherein said fusion polypeptide comprises a heterologous antigen fused to an N-terminal LLO, wherein said recombinant Listeria is an attenuated Listeria comprising a mutation in the dal/dat genes, wherein said Listeria comprises an episomal vector comprising a nucleic acid sequence encoding a metabolic enzyme that complements said dal/dat mutation, wherein said episomal vector is stably maintained in said recombinant Listeria in the absence of antibiotic selection, and wherein said Listeria comprises a deletion of the endogenous actA gene. 2. The recombinant Listeria of claim 1, wherein said nucleic acid molecule is integrated into the Listeria genome. 3. The recombinant Listeria of claim 1, wherein said nucleic acid molecule is in said episomal vector in said recombinant Listeria strain. 4. The recombinant Listeria of claim 3, wherein said episomal vector does not confer antibiotic resistance upon said recombinant Listeria. 5. The recombinant Listeria of claim 1, wherein said metabolic enzyme is an alanine racemase enzyme or a D-amino acid transferase enzyme. 6. The recombinant Listeria of claim 1, wherein the heterologous antigen is Prostate Specific Antigen (PSA) or a fragment thereof, or Human Papilloma Virus E7 (HPV-E7) or a fragment thereof. 7. An immunogenic composition comprising the recombinant Listeria of claim 6, and an adjuvant. 8. The recombinant Listeria of claim 7, wherein said adjuvant comprises a granulocyte/macrophage colony-stimulating factor (GM-CSF) protein, a nucleic acid molecule encoding a GM-CSF protein, saponin QS21, monophosphoryl lipid A, or an unmethylated CpG-containing oligonucleotide. 9. The recombinant Listeria of claim 1, wherein said Listeria is a Listeria monocytogenes strain. 10. A recombinant Listeria strain comprising a nucleic acid molecule encoding a fusion polypeptide, wherein said fusion polypeptide comprises a Prostate Specific Antigen (PSA) or fragment thereof fused to an N-terminal LLO, wherein said recombinant Listeria is an attenuated Listeria comprising a mutation in the dal/dat genes, wherein said Listeria comprises a metabolic enzyme that complements said dal/dat mutation, and wherein said Listeria comprises a deletion of the endogenous actA gene.
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