Polypeptides isolated from
View Patent ↗The present invention relates to methods and pharmaceutical compositions for treating cancer. More specifically, the invention relates to a polypeptide isolated from Brevibacterium aurantiacum that shows methionine gamma-lyase and homocysteinase activities. The present invention also relates to the use of such a polypeptide for the treatment of cancer.
1. A vector comprising a nucleic acid encoding a polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof.
2. The vector of claim 1 , wherein the nucleic acid encoding for a polypeptide is selected from the group consisting of SEQ ID NO: 2 and SEQ ID NO: 3.
3. A nucleic acid encoding a recombinant polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof.
4. The nucleic acid according to claim 3 comprising a sequence as set forth by SEQ ID NO: 2.
5. The nucleic acid according to claim 3 comprising a sequence as set forth by SEQ ID NO: 3.
6. A host cell, which has been transformed by
a nucleic acid encoding a recombinant polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof and/or
a vector comprising a nucleic acid encoding a polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof.
7. A pharmaceutical composition comprising
i) a recombinant polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof, or a nucleic acid encoding a polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof, or a vector comprising said nucleic acid, and
ii) a pharmaceutically acceptable carrier.
8. The pharmaceutical composition according to claim 7 comprising one or more enzyme cofactors.
9. The pharmaceutical composition according to claim 7 comprising one or more chemotherapeutic or radiotherapeutic agents.
10. A recombinant polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof contained in a vector.
11. A polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof which is covalently conjugated with at least one polyethylene glycol group.
12. A polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof which is covalently coupled to a tumor targeting agent.
13. A method of producing a polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1, which method comprises the steps of:
i) culturing a host cell transformed by
a) a nucleic acid encoding a recombinant polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof,
and/or
b) a vector comprising a nucleic acid encoding a polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof,
under condition suitable to allow expression of said polypeptide; and
(ii) recovering the expressed polypeptide.
14. A method for treating a cancer in a subject of need thereof comprising the step of administering to said subject a polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof.
15. A method for treating a cancer in a subject of need thereof comprising the step of administering to said subject a nucleic acid encoding a polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof, or a vector comprising said nucleic acid.
16. A method for treating a cancer in a subject of need thereof comprising the step of administering to said subject a combination of
i) a polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof, or a nucleic acid encoding a polypeptide comprising an amino acid sequence as set forth by SEQ ID NO: 1 or a functionally-conservative variant thereof, or a vector comprising said nucleic acid, and
ii) one or more agents selected from the group consisting of: one or more enzyme cofactors and one or more chemotherapeutic or radiotherapeutic agents.