Methods and therapeutic compositions for treating cancer

• US 20020045591A1
• Filed: 07/17/2001
• Published: 04/18/2002
• Est. Priority Date: 05/26/1998
• Status: Abandoned Application

• Current Assignee: Benjamin Geiger, Ben-Zeʼev, Avri, Einat Sadot
• Original Assignee: Benjamin Geiger, Ben-Zeʼev, Avri, Einat Sadot
• Inventors: Sadot, Einat, Geiger, Benjamin, Ben-Zeʼev, Avri
• Application Number:
  US09/905,983
• Publication Number:
  US 20020045591A1
• Time in Patent Office: Days
• US Class Current: 514/44
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748

Abstract

Methods and therapeutic compositions for the treatment of cancer are disclosed. Specifically, peptides including β-catenin binding domains and polynucleotide sequences encoding same, such as cadherins and o-catenins and polynucleotide sequences encoding same, effective in methods and compositions for treating cancers associated with abnormally high levels of β-catenin, such as colon cancers and melanomas.

Claims

1. A pharmaceutical composition for treatment of cancer associated with abnormally high activity levels of β

-catenin comprising a pharmaceutically acceptable gene therapy vehicle harboring a polynucleotide that comprises;

(a) a first nucleotide sequence encoding a soluble cytoplasmic portion of a cadherin, said soluble cytoplasmic portion of said cadherin lacking a transmembrane portion and an extracellular portion of said cadherin and including a β

-catenin binding domain; and

(b) a second nucleotide sequence being positioned upstream of said first nucleotide sequence and containing a promoter for directing expression of said soluble cytoplasmic portion of said cadherin in a mammalian cell;

said acceptable gene therapy vehicle being therapeutically effective in reducing the abnormally high activity levels of β

-catenin.

2. The pharmaceutical composition of claim 1, wherein said cadherin is selected from the group consisting of E-cadherin, N-cadherin, P-cadherin and VE-cadherin.

3. The pharmaceutical composition of claim 1, wherein said first nucleotide sequence is derived from SEQ ID NOs. 1, 4, 45, 47, 49 or 51.

4. The pharmaceutical composition of claim 1, wherein said first nucleotide sequence encodes, at most, about 70 amino acids of a cadherin.

5. The pharmaceutical composition of claim 1, wherein said cadherin is from a species selected from the group consisting of human, chicken, xenopus, mouse, canine and drosophila.

6. The pharmaceutical composition of claim 1, wherein said cadherin is human.

8. A pharmaceutical composition for treatment of cancer associated with abnormally high activity levels of β

-catenin comprising a pharmaceutically acceptable gene therapy vehicle harboring a polynucleotide that comprises;

(a) a first nucleotide sequence encoding an o-catenin; and

(b) a second nucleotide sequence being positioned upstream of said first nucleotide sequence and containing a promoter for directing expression of said o-catenin in a mammalian cell;

said acceptable gene therapy vehicle being therapeutically effective in reducing the abnormally high activity levels of β

-catenin.

9. The pharmaceutical composition of claim 8, wherein said o-catenin is from human.

10. A method of treating cancer associated with abnormally high activity levels of β

-catenin comprising administering to a subject in need a pharmaceutically acceptable gene therapy vehicle harboring a polynucleotide that comprises;

(a) a first nucleotide sequence encoding a soluble cytoplasmic portion of a cadherin, said soluble cytoplasmic portion of said cadherin lacking a transmembrane portion and an extracellular portion of said cadherin and including a β

-catenin binding domain; and

(b) a second nucleotide sequence being positioned upstream of said first nucleotide sequence and containing a promoter for directing expression of said soluble cytoplasmic portion of said cadherin in a mammalian cell;

said acceptable gene therapy vehicle being therapeutically effective in reducing the abnormally high activity levels of β

-catenin.

7. The pharmaceutical composition of claim 10, wherein said cytoplasmic portion of said cadherin is signal peptide-free.

11. The method of claim 10, wherein said cadherin is selected from the group consisting of E-cadherin, N-cadherin, P-cadherin and VE-cadherin.

12. The method of claim 10, wherein said first nucleotide sequence is derived from SEQ ID NOs. 1, 4, 45, 47, 49 or 51.

13. The method of claim 10, wherein said first nucleotide sequence encodes, at most, about 70 amino acids of a cadherin.

14. The method of claim 10, wherein said cadherin is from a species selected from the group consisting of human, chicken, xenopus, mouse, canine and drosophila.

15. The method of claim 10, wherein said cadherin is human.

16. The method of claim 10, wherein said cytoplasmic portion of said cadherin is signal peptide-free.

18. The method of claim 17, wherein said o-catenin is from human.

20. The method of claim 19, wherein said cadherin is selected from the group consisting of E-cadherin, N-cadherin, P-cadherin and VE-cadherin.

21. The method of claim 19, wherein said first nucleotide sequence is derived from SEQ ID NOs. 1, 4, 45, 47, 49 or 51.

22. The method of claim 19, wherein said first nucleotide sequence encodes, at most, about 70 amino acids of a cadherin.

23. The method of claim 19, wherein said cadherin is from a species selected from the group consisting of human, chicken, xenopus, mouse, canine and drosophila.

24. The method of claim 19, wherein said cadherin is human.

25. The method of claim 19, wherein said cytoplasmic portion of said cadherin is signal peptide-free.

27. The method of claim 26, wherein said o-catenin is from human.

17. A method of treating cancer associated with abnormally high activity levels of β

-catenin comprising administering to a subject in need a pharmaceutically acceptable gene therapy vehicle harboring a polynucleotide that comprises;

(a) a first nucleotide sequence encoding an o-catenin; and

(b) a second nucleotide sequence being positioned upstream of said first nucleotide sequence and containing a promoter for directing expression of said c-catenin in a mammalian cell;

said acceptable gene therapy vehicle being therapeutically effective in reducing the abnormally high activity levels of β

-catenin.

19. A method reducing abnormally high activity levels of β

-catenin is mammalian cells comprising infecting or transforming the cells with a vehicle harboring a polynucleotide that comprises;

(a) a first nucleotide sequence encoding a soluble cytoplasmic portion of a cadherin, said soluble cytoplasmic portion of said cadherin lacking a transmembrane portion and an extracellular portion of said cadherin and including a β

-catenin binding domain; and

(b) a second nucleotide sequence being positioned upstream of said first nucleotide sequence and containing a promoter for directing expression of said soluble cytoplasmic portion of said cadherin in a mammalian cell;

said vehicle being effective in reducing the abnormally high activity levels of β

-catenin in the cells.

26. A method reducing abnormally high activity levels of β

-catenin is mammalian cells comprising infecting or transforming the cells with a vehicle harboring a polynucleotide that comprises;

(a) a first nucleotide sequence encoding an o-catenin; and

(b) a second nucleotide sequence being positioned upstream of said first nucleotide sequence and containing a promoter for directing expression of said o-catenin in a mammalian cell;

said vehicle being effective in reducing the abnormally high activity levels of β

-catenin in the cells.