Adenovirus E1A fragments for use in anti-cancer therapies
View Patent ↗The present invention relates to an improved cancer therapy comprising co-administration with the E1A 1-80 transcription-repression domain activity. In addition, E1A 1-80 can act as a monotherapy against cancers that express elevated HER2/Neu or in combination with anti-HER2/Neu, chemo- or radiotherapeutic treatments.
1. A method of inhibiting a cancer cell comprising contacting said cancer cell with a polypeptide characterized as:
(a) comprising residues 1-80 of adenovirus E1A (SEQ ID NO: 1);
(b) substantially lacking E1A sequences C-terminal to residue 80; and
(c) comprising a non-E1A stabilization sequence located C-terminal to residue 80.
2. The method of claim 1 , wherein said cancer cell overexpresses HER2-Neu as compared to a non-cancer cell.
3. The method of claim 1 , wherein said cancer cell does not overexpress HER2-Neu as compared to a non-cancer cell.
4. The method of claim 1 , wherein said cancer cell is a breast cancer cell.
5. The method of claim 1 , wherein said cancer cell is a lung cancer cell, an ovarian cancer cell, a brain cancer cell, or a prostate cancer cell.
6. The method of claim 1 , wherein said cancer cell is a carcinoma, an adenocarcinoma or a glioblastoma.
7. The method of claim 1 , wherein said non-E1A stabilization sequence is about 40 residues in length.
8. The method of claim 4 , wherein said non-E1A stabilization sequence comprises residues 14-27 of SEQ ID NO: 3 or residues 1-27 of SEQ ID NO: 3.
9. The method of claim 4 , wherein said non-E1A stabilization sequence comprises of SEQ ID NO: 3.
10. The method of claim 1 , wherein said polypeptide lacks E1A sequences other than SEQ ID NO: 1.
11. The method of claim 1 , wherein contacting comprises introducing into said cell a viral vector comprising a polynucleotide segment encoding said polypeptide under the control of a promoter active in said cell.
12. The method of claim 1 , wherein contacting comprises introducing into said cell a non-viral vector comprising an polynucleotide segment encoding said polypeptide under the control of a promoter active in said cell.
13. The method of claim 12 , wherein said non-viral vector is delivered in a lipid delivery vehicle.
14. The method of claim 1 , wherein said polypeptide further comprises a cell penetrating domain.
15. The method of claim 1 , further comprising contacting said cancer cell with a second anti-cancer treatment.
16. The method of claim 1 , further comprising contacting said polypeptide with said cancer cell at least a second time.
17. The method of claim 1 , wherein said cancer cell is a multi-drug resistant cancer cell.
18. The method of claim 1 , wherein inhibiting comprises slowing the growth of said cancer cell.
19. The method of claim 1 , wherein inhibiting comprises killing said cancer cell.
20. The method of claim 17 , wherein killing comprises inducing apoptosis in said cancer cell.
21. The method of claim 1 , further comprises assessing HER2-Neu expression prior to contacting.
22. A method of treating a subject with cancer comprising contacting a cancer cell in said subject with an polypeptide characterized as:
(a) comprising residues 1-80 of adenovirus E1A (SEQ ID NO: 1);
(b) substantially lacking E1A sequences C-terminal to residue 80; and
(c) comprising a non-E1A stabilization sequence located C-terminal to residue 80.
23. A method of increasing remission time in a subject with cancer that is in remission comprising contacting a cancer cell in said subject with an polypeptide characterized as:
(a) comprising residues 1-80 of adenovirus E1A (SEQ ID NO: 1);
(b) substantially lacking E1A sequences C-terminal to residue 80; and
(c) comprising a non-E1A stabilization sequence located C-terminal to residue 80.