Treatment for cancer
AssigneeThe University of Nottingham
InventorsNigel Peter Minton, John Timothy Heap
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Abstract
The present invention provides a method of treatment for cancer in a subject comprising the administration of a prodrug, wherein the subject is colonised with an obligate anaerobic microorganism capable of expressing a polypeptide having nitroreductase activity, wherein the polypeptide exhibits preferential reduction of CB1954 to a 4-hydroxylamine (4HX) derivative instead of a 2-hydroxylamine derivative; and is capable of reducing CB1954 to the 4HX derivative with a Km of less than 30 micromolar. The present invention further provides an isolated polypeptide, nucleic acids encoding said polypeptide, vectors and host cells comprising said nucleic acids and vectors and uses of the above in treating solid tumours.
Claims18
A method of treating a solid tumor cancer in a subject comprising the administration to the subject of an obligate anaerobic microorganism expressing a polypeptide having nitroreductase activity and/or the spores thereof, wherein the obligate anaerobic microorganism and/or spores thereof colonize a tumour of the subject, and wherein the polypeptide:
- exhibits preferential reduction of CB1954 to a 4-hydroxylamine (4HX) derivative instead of a 2-hydroxylamine derivative;
- and
- is capable of reducing CB1954 to the 4HX derivative with a Km of less than 30 micromolar;
- and
- wherein the polypeptide comprises or consists of the amino acid sequence of:
- a. SEQ ID NO:
- 1 (NmeNTR);
- or
- b. SEQ ID NO:
- 2 (HsoNTR).
A method of converting a prodrug to a drug active in situ in a tumour, such as a solid tumour in a subject in need thereof, comprising administering an obligate anaerobic microorganism and/or the spores thereof to the subject, wherein the obligate anaerobic microorganism and/or spores thereof expresses a polypeptide having nitroreductase activity, wherein the polypeptide:
- exhibits preferential reduction of CB1954 to a 4-hydroxylamine (4HX) derivative instead of a 2-hydroxylamine derivative;
- and
- is capable of reducing CB1954 to the 4HX derivative with a Km of less than 30 micromolar;
- and
- wherein the polypeptide comprises or consists of the amino acid sequence of:
- a. SEQ ID NO:
- 1 (NmeNTR);
- or
- b. SEQ ID NO:
- 2 (HsoNTR).
Dependencies are inferred from the claim text.