Compositions and methods for treatment of cervical dysplasia
View Patent ↗The present invention provides methods of treating, protecting against, and inducing an immune response against cervical dysplasia and cancer, comprising the step of administering to a subject a recombinant Listeria strain, comprising a fusion peptide that comprises an LLO fragment and an E7 and/or E6 antigen. The present invention also provides methods for inducing an anti-E7 CTL response in a human subject and treating HPV-mediated diseases, disorders, and symptoms, comprising administration of the recombinant Listeria strain.
1. A method of treating cervical dysplasia in a human subject, the method comprising the step of administering to said subject a recombinant Listeria strain, said recombinant Listeria strain comprising a recombinant polypeptide comprising an N-terminal fragment of an LLO protein, comprising the sequence of SEQ ID NO:1, fused to a Human Papilloma Virus (HPV) E7 antigen, thereby treating a cervical dysplasia in a human subject.
2. The method of claim 1 , wherein said administering is intravenous administering.
3. The method of claim 1 , wherein said recombinant Listeria strain is administered to said human subject at a dose of 5.10 7 , 3.3×10 8 or from 1×10 9 to 1×10 10 organisms.
4. The method of claim 1 , wherein said recombinant Listeria strain is a recombinant Listeria monocytogenes strain.
5. The method of claim 1 , wherein said recombinant Listeria strain has been passaged through an animal host, prior to the step of administering.
6. The method of claim 1 , wherein said recombinant polypeptide is expressed by said recombinant Listeria strain.
7. The method of claim 1 , wherein said recombinant Listeria strain comprises a plasmid that encodes said recombinant polypeptide.
8. The method of claim 7 , wherein said plasmid comprises a gene encoding a bacterial transcription factor.
9. The method of claim 7 , wherein said plasmid comprises a gene encoding a metabolic enzyme.
10. The method of claim 1 , further comprising the step of boosting said human subject with said recombinant Listeria strain.
11. The method of claim 1 , further comprising the step of inoculating said human subject with an immunogenic composition that comprises said E7 antigen.
12. The method of claim 1 , wherein said recombinant Listeria strain has been stored in a frozen or lyophilized cell bank.
13. The method of claim 12 , wherein said recombinant Listeria strain exhibits viability upon thawing or reconstitution of greater than 90%.
14. A method of inducing an immune response against a cervical dysplasia in a human subject, the method comprising the step of administering to said subject a recombinant Listeria strain, said recombinant Listeria strain comprising a recombinant polypeptide comprising an N-terminal fragment of an LLO protein, comprising the sequence of SEQ ID NO: 1, fused to a Human Papilloma Virus (HPV) E7 antigen, thereby inducing an immune response against a cervical dysplasia in a human subject.
15. The method of claim 14 , wherein said administering is intravenous administering.
16. The method of claim 14 , wherein said recombinant Listeria strain is administered to said human subject at a dose of 5.10 7 , 3.3×10 8 or from 1×10 9 to 1×10 10 organisms.
17. The method of claim 14 , wherein said recombinant Listeria strain is a recombinant Listeria monocytogenes strain
18. The method of claim 14 , wherein said recombinant Listeria strain has been passaged through an animal host, prior to the step of administering.
19. The method of claim 14 , wherein said recombinant polypeptide is expressed by said recombinant Listeria strain.
20. The method of claim 14 , wherein said recombinant Listeria strain comprises a plasmid that encodes said recombinant polypeptide.
21. The method of claim 20 , wherein said plasmid expresses a Listeria transcription factor.
22. The method of claim 20 , wherein said plasmid comprises a gene encoding a metabolic enzyme.
23. The method of claim 14 , further comprising the step of boosting said human subject with said recombinant Listeria strain.
24. The method of claim 14 , further comprising the step of inoculating said human subject with an immunogenic composition that comprises said E7 antigen.
25. The method of claim 14 , wherein said recombinant Listeria strain has been stored in a frozen or lyophilized cell bank.
26. The method of claim 25 , wherein said recombinant Listeria strain exhibits viability upon thawing or reconstitution of greater than 90%.