Methods and compositions for detection of microorganisms and cells and treatment of diseases and disorders

• US 7,820,184 B2
• Filed: 01/11/2008
• Issued: 10/26/2010
• Est. Priority Date: 07/11/2006
• Status: Expired due to Fees

• Current Assignee: Genelux Corporation
• Original Assignee: Genelux Corporation
• Inventors: Szalay, Aladar A., Yu, Yong A., Hill, Phil, Stritzker, Jochen Harald
• Primary Examiner(s): Swartz; Rodney P.
• Application Number:
  US12/008,659
• Publication Number:
  US 20090180987A1
• Time in Patent Office: 1,019 Days
• Field of Search: 424/9.1, 424/9.2, 424/234.1, 424/241.1, 435/4, 435/8, 435/29
• US Class Current: 424/241.1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/242 Gold; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 33/244 Lanthanides; Compounds thereof medicinal preparations containing radioactive lanthanides for use in therapy or testing in vivo A61K51/00
• CPC Class Codes: A61K 33/26 Iron; Compounds thereof
• CPC Class Codes: A61K 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: G01N 2333/245 Escherichia (G)
• CPC Class Codes: G01N 33/56916 Enterobacteria, e.g. shigella, salmonella, klebsiella, serratia
• CPC Class Codes: G01N 33/57484 involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites

Abstract

Methods for detecting a microorganism or cell in a subject and methods for detecting, imaging or diagnosing a site, disease, disorder or condition in a subject using microorganisms or cells and methods that microorganisms or cells for treating a disease, disorder or condition are provided. Sites, diseases and disorders include sites of cell proliferation, proliferative conditions, neoplasms, tumors, neoplastic disease, wounds and inflammation. Also provided are microorganisms and cells for use in the methods and compositions, combinations and kits, including diagnostic and pharmaceutical compositions, containing a microorganism or cell.

Claims

1. A method for converting a prodrug to an active form, comprising:

administering a Nissle strain Escherichia coli bacteria to a subject, wherein Nissle bacterium encodes a prodrug converting enzyme for converting a prodrug into an active form; and

administering a prodrug that is converted by the enzyme, whereby an active form of the prodrug is produced.

2. The method of claim 1, wherein an active form of the prodrug is a cytotoxin.

3. The method of claim 1, wherein the Nissle bacterium is administered systemically.

4. The method of claim 1, wherein the Nissle bacterium is administered intravenously.

5. The method of claim 1, wherein the prodrug is administered intravenously.

6. The method of claim 1, wherein the prodrug is selected from among 5-fluorouracil, gancyclovir, 6-methylpurine deoxyriboside, cephalosporin-doxorubicin, 4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl-L-glutamic acid, indole-3-acetic acid, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin, bis-(2-chloroethyl)amino-4-hydroxyphenylaminomethanone 28, 1-chloromethyl-5-hydroxy-1,2-dihydro-3H-benz[e]indole, epirubicin-glucoronide, 5′

-deoxy-5-fluorouridine, cytosine arabinoside and linamarin.

7. The method of claim 1, wherein the prodrug converting enzyme is selected from among thymidine kinase, cytosine deaminase, purine nucleoside phosphorylase, beta lactamase, carboxypeptidase G2, cytochrome P450, horseradish peroxidase, nitroreductase, carboxylesterase, tyrosinase, beta galactosidase, beta glucuronidase, thymidine phosphorylase, deoxycytidine kinase and linamerase.

8. The method of claim 1, wherein the prodrug converting enzyme is endogenous to the Nissle bacterium.

9. The method of claim 1, wherein:

expression of the gene encoding the prodrug converting enzyme is directed by an inducible promoter, and the method further comprises administering to the subject an inducer molecule, whereby the inducible promoter is activated.

10. The method of claim 9, wherein the inducible promoter is selected from among IPTG-, antibiotic-, heat-, pH-, light-, metal-, aerobic-, host cell-, drug-, cell cycle-, sugar and tissue specific-inducible promoters.

11. The method of claim 9, wherein the inducible promoter is an arabinose-inducible promoter or a xylose-inducible promoter.

12. The method of claim 11, wherein:

the inducible promoter is an arabinose-inducible promoter;

and the inducer molecule is arabinose.

13. The method of claim 11, wherein the inducer molecule is arabinose or xylose.

14. The method of claim 9, wherein the inducer molecule is administered systemically.

15. The method of claim 9, wherein the inducer molecule is administered intravenously or orally.

16. The method of claim 11, wherein one or more genes in the Nissle bacterium are modified, whereby the Nissle bacterium does not metabolize L-arabinose.

17. The method of claim 1, wherein the prodrug and enzyme are selected from among Herpes simplex virus thymidine kinase/gancyclovir, varicella zoster thymidine kinase/gancyclovir, cytosine deaminase/5-fluorouracil, purine nucleoside phosphorylase/6-methylpurine deoxyriboside, beta lactamase/cephalosporin-doxorubicin, carboxypeptidase G2/4-[(2-chloroethyl)(2-mesyloxyethyl)-amino]benzoyl-L-glutamic acid, cytochrome P450/acetaminophen, horseradish peroxidase/indole-3-acetic acid, nitroreductase/CB1954, rabbit carboxylesterase/7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin, mushroom tyrosinase/bis-(2-chloroethyl)amino-4-hydroxyphenylaminomethanone 28, beta galactosidase/1-chloromethyl-5-hydroxy-1,2-dihydro-3H-benz[e]indole, beta glucuronidase/epirubicin-glucoronide, glucuronidase/glucuronyldoxorubicin, thymidine phosphorylase/5′

-deoxy-5-fluorouridine, deoxycytidine kinase/cytosine arabinoside, beta-lactamase and linamerase/linamarin.

18. The method of claim 1, wherein the subject has a tumor and conversion of the prodrug results in a form that is active against the tumor.