Use of plant cells expressing a TNFalpha polypeptide inhibitor in therapy
A method of treating a TNF Alpha associated medical condition selected from the group consisting of obesity, metabolic syndrome, diabetes and a liver disease or disorder is provided. The method comprising enterally administering to a subject in need thereof a therapeutically effective amount of plant cells expressing a TNF Alpha polypeptide inhibitor, thereby treating the TNF Alpha associated medical condition.
1. A method of treating a TNFα associated liver disease or disorder, the method comprising enterally administering to a subject in need thereof a therapeutically effective amount of plant cells expressing a TNFα polypeptide inhibitor, wherein said TNFα polypeptide inhibitor is a chimeric polypeptide comprising:
(i) a first domain comprising a TNFα binding domain of TNFR2; and
(ii) a second domain comprising an Fc domain of an immunoglobulin,
wherein the chimeric polypeptide is TNFR2:Fc,
thereby treating the TNFα associated liver disease or disorder.
2. The method of claim 1 , wherein said enteral is oral administration.
3. The method of claim 1 , wherein
the carboxy terminus of said first domain is translationally fused to the N-terminus of the second domain and wherein the chimeric polypeptide specifically binds TNFα.
4. The method of claim 3 , wherein said chimeric polypeptide further comprises a third domain which comprises an endoplasmic reticulum retention signal, wherein the carboxy terminus of the second domain is translationally fused to the N-terminus of the third domain.
5. The method of claim 3 , comprising an additional domain encoding an endoplasmic reticulum signal peptide, wherein the carboxy terminus of the endoplasmic reticulum signal peptide is translationally fused to the N-terminus of said first domain.
6. The method of claim 5 , wherein said signal peptide is a plant signal peptide.
7. The method of claim 6 , wherein said plant signal peptide is set forth in the amino acid sequence of SEQ ID NO: 4.
8. The method of claim 3 , wherein said first domain is 200-250 amino acids long.
9. The method of claim 8 , wherein said first domain comprises the amino acid sequence LCAP (SEQ ID NO: 11) and VFCT (SEQ ID NO: 12).
10. The method of claim 9 , wherein said first domain further comprises the amino acid sequence LPAQVAFXPYAPEPGSTC (SEQ ID NO: 13).
11. The method of claim 10 , wherein said first domain is set forth in the amino acid sequence of SEQ ID NO: 2.
12. The method of claim 3 , wherein said second domain is set forth in the amino acid sequence of SEQ ID NO: 9.
13. The method of claim 3 , wherein said chimeric polypeptide is set forth in the amino acid sequence of SEQ ID NO: 6.
14. The method of claim 4 , wherein said chimeric polypeptide is set forth in the amino acid sequence of any one of SEQ ID NO: 7, 204 or 205.
15. The method of claim 3 , wherein said chimeric polypeptide is capable of inhibiting TNFα-induced apoptosis.
16. The method of claim 1 , wherein said TNFα polypeptide inhibitor comprises a plant-specific glycan.
17. The method of claim 1 , wherein said plant cells are Nicotiana tabacum plant cells.
18. The method of claim 17 , wherein said Nicotiana tabacum plant cell is a Bright Yellow (BY-2) cell.
19. The method of claim 1 , wherein said plant cells are lyophilized.
20. The method of claim 1 , wherein said plant cells are grown in suspension.
21. The method of claim 1 , wherein said liver disease or disorder is selected from the group consisting of hepatitis, liver cirrhosis, liver cancer, hepatotoxicity, chronic liver disease, fatty liver disease and non-alcoholic steatohepatitis (NASH).
22. The method of claim 1 , wherein said plant cells are provided in an oral nutritional form.
23. The method of claim 1 , wherein said TNFα polypeptide inhibitor reduces a serum enzyme or a metabolite.
24. The method of claim 4 , wherein said chimeric polypeptide is set forth in the amino acid sequence of SEQ ID NO: 7.