CA2342040A1 - Anaerobic bacterium as a drug for cancer gene therapy - Google Patents
Anaerobic bacterium as a drug for cancer gene therapy Download PDFInfo
- Publication number
- CA2342040A1 CA2342040A1 CA002342040A CA2342040A CA2342040A1 CA 2342040 A1 CA2342040 A1 CA 2342040A1 CA 002342040 A CA002342040 A CA 002342040A CA 2342040 A CA2342040 A CA 2342040A CA 2342040 A1 CA2342040 A1 CA 2342040A1
- Authority
- CA
- Canada
- Prior art keywords
- bacterium
- dna
- protein
- antitumor substance
- antitumor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
Abstract
The present invention provides a bacterium belonging to the genus Bifidobacterium, by which DNA coding for a protein having an antitumor activity or DNA coding for a protein having the activity of converting a precursor of an antitumor substance into the antitumor substance is delivered to tumor tissues specifically under anaerobic conditions thereby expressing the protein encoded by the DNA, as well as a pharmaceutical composition comprising said anaerobic bacterium.
Claims (27)
1. A method for delivering a gene in a system for delivering DNA specifically to tumor tissues under anaerobic conditions, wherein a bacterium belonging to the genus Bifidobacterjum is used as a gene delivery vector and then the DNA delivered specifically to tumor tissues under anaerobic conditions is expressed in said tumor tissues.
2. A method for delivering a gene in a system for delivering DNA specifically to tumor tissues under anaerobic conditions, wherein a bacterium belonging to the genus Bifidobacterium and having the DNA coding for a protein which has a higher activity than in its parent strain is used as a gene delivery vector and then the DNA delivered specifically to tumor tissues under anaerobic conditions is expressed in said tumor tissues.
3. A method for delivering a gene in a system for delivering DNA specifically to tumor tissues under anaerobic conditions, wherein a bacterium belonging to the genus Bifidobacterium transformed with a recombinant DNA having said DNA is used as a gene delivery vector and the DNA delivered specifically to tumor tissues under anaerobic conditions is expressed in the tumor tissues.
4. The method as claimed in any one of Claims 1 to 3, wherein the DNA is selected from the group consisting of:
(a) DNA coding for a protein having an antitumor activity, and (b) DNA coding for a protein having an activity of converting a precursor of an antitumor substance into the antitumor substance.
(a) DNA coding for a protein having an antitumor activity, and (b) DNA coding for a protein having an activity of converting a precursor of an antitumor substance into the antitumor substance.
5. The method as claimed in Claim 4, wherein the protein having an antitumor activity is interleukin-2.
6. The method as claimed in Claim 4, wherein the precursor of an antitumor substance is selected from the group consisting of 5-fluorocytosine, 5-aziridino-2,4-dinitrobenzamide, ganciclovir, a glucuronic acid-conjugated antitumor substance and a lysine-conjugated antitumor substance.
7. The method as claimed in Claim 4 , wherein the protein having the activity of converting a precursor of an antitumor substance into the antitumor substance is a protein selected from the group consisting of cytosine deaminase, nitroreductase, herpes simplex virus type 1 thymidine kinase and .beta.-glucuronidase.
8. The method as claimed in Claim 3, wherein the recombinant DNA is an expression vector.
9. The method as claimed in Claim 8, wherein the expression vector has a promoter and a terminator functioning in a bacterium belonging to the genus Bifidobacterium.
10. The method as claimed in Claim 9, wherein the promoter and terminator are those involved in expressing a gene coding for histone-like DNA-binding protein(HU protein) derived from Bjfidobacterjum longum.
11. The method as claimed in Claim 9, wherein the promoter and terminator are DNAs located at the 1- to 192-positions and at the 472- to 600-positions respectively in the nucleotide sequence set forth in SEQ ID NO: 1.
12. The method as claimed in any one of Claims 1 to 11, wherein the bacterium is Bifidobacterium longum.
13. The method as claimed in any one of Claims 1 to 4 or 6 to 12, wherein the bacterium is Bifidobacterium longum 105-A/pBLES100-S-eCD (FERM BP-7274).
14. A method for expressing a gene coding for a protein having an antitumor activity in tissue tumors specifically, which comprises use of the bacterium as claimed in any one of Claims 1 to 5 or 8 to 12.
15. A method for expressing a gene coding for a protein having the activity of converting a precursor of an antitumor substance into the antitumor substance in tissue tumors specifically, which comprises use of the bacterium as claimed in any one of Claims 1 to 4 or 6 to 12.
16. A pharmaceutical composition comprising the bacterium as claimed in any one of Claims 1 to 13.
17. The pharmaceutical composition as claimed in Claim 16, wherein the pharmaceutical composition comprises a combination of the bacterium as claimed in any one of Claims 1 to 4 or 6 to 13 and the precursor of an antitumor substance.
18. The pharmaceutical composition as claimed in Claim 16, wherein the pharmaceutical composition comprises the bacterium as claimed, in any one of Claims 1 to 4 or 6 to 13 and the precursor of an antitumor substance.
19. The pharmaceutical composition as claimed in any one of Claims 16 to 18, wherein the bacterium is Bifidobacterium longum.
20. The pharmaceutical composition as claimed in any one of Claims 16 to 19, wherein bacterium is Bifidobacterium longum 105-A/pBLES100-S-eCD (FERM BP-7274).
21. A bacterium belonging to the genus Bifidobacterium, which is used in the method as claimed in any one of Claims 1 to 13.
22. Bifidobacterium longum 105-A/pBLES100-S-eCD (FERM
BP-7274.
BP-7274.
23. DNA having the nucleotide sequence set forth in SEQ
ID NO: 1.
ID NO: 1.
24. A method of treating a solid tumor, which comprises use of the method as claimed in any one of Claims 1 to 15.
25. A method of treating a solid tumor, which comprises administering the bacterium as claimed in any one of Claims 1 to 4 or 6 to 13 in combination with the precursor of an antitumor substance.
26. An anaerobic bacterium belonging to the genus Bifidobacterium capable of expressing a gene coding for a protein having an antitumor activity in only cancer cells under substantially anaerobic conditions.
27. An anaerobic bacterium belonging to the genus Bifidobacterium capable of expressing a gene coding for a protein having the activity of converting a precursor of an antitumor substance with low toxicity to humans and animals into an antitumor substance in only cancer cells under substantially anaerobic conditions.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP287688/2000 | 2000-09-21 | ||
JP2000287688 | 2000-09-21 |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2342040A1 true CA2342040A1 (en) | 2002-03-21 |
CA2342040C CA2342040C (en) | 2012-07-10 |
Family
ID=18771403
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2342040A Expired - Lifetime CA2342040C (en) | 2000-09-21 | 2001-03-26 | Anaerobic bacterium as a drug for cancer gene therapy |
Country Status (2)
Country | Link |
---|---|
US (2) | US20020054865A1 (en) |
CA (1) | CA2342040C (en) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1281767A3 (en) | 2001-07-31 | 2003-05-28 | Aladar A. Szalay | Light emitting microorganisms and cells for diagnosis and therapy of tumors |
US20030228261A1 (en) * | 2002-06-05 | 2003-12-11 | Aladar Szalay | Light emitting microorganisms and cells for diagnosis and therapy of diseases associated with wounded or inflamed tissue |
EP1369491A1 (en) * | 2002-06-05 | 2003-12-10 | Aladar A. Szalay | Light emitting microorganisms and cells for diagnosis and therapy of diseases associated with wounded or inflamed tissue |
ATE420160T1 (en) | 2003-06-18 | 2009-01-15 | Genelux Corp | MODIFIED RECOMBINANT VACCINIA VIRUSES, USES THEREOF |
US20070270504A1 (en) * | 2003-06-20 | 2007-11-22 | Avalon Pharmaceuticals, Inc. | Identification of Therapeutic Agents Using Genetic Fingerprinting |
DE602005025946D1 (en) | 2004-11-24 | 2011-02-24 | Anaeropharma Science Inc | New shuttle vector |
US8734779B2 (en) * | 2005-04-08 | 2014-05-27 | Anaeropharma Science Inc. | 5-fluorouracil-resistant bacteria and method for production thereof |
TW200819540A (en) | 2006-07-11 | 2008-05-01 | Genelux Corp | Methods and compositions for detection of microorganisms and cells and treatment of diseases and disorders |
EP2242516A1 (en) * | 2008-01-11 | 2010-10-27 | Genelux Corporation | Methods and compositions for detection of bacteria and treatment of diseases and disorders |
US9730968B2 (en) | 2008-04-17 | 2017-08-15 | Anaeropharma Science, Inc. | Therapeutic agent for ischemic diseases |
ES2628378T3 (en) * | 2008-04-17 | 2017-08-02 | Anaeropharma Science, Inc. | Plasmid vector |
ES2569659T3 (en) | 2009-09-17 | 2016-05-12 | Morishita Jintan Co., Ltd. | Gene expressing a fusion protein presented on the surface of bifidobacterium |
CA2787787A1 (en) * | 2010-01-29 | 2011-08-04 | Anaeropharma Science, Inc. | Transformation plasmid |
WO2012008860A2 (en) | 2010-07-16 | 2012-01-19 | Auckland Uniservices Limited | Bacterial nitroreductase enzymes and methods relating thereto |
US9616114B1 (en) | 2014-09-18 | 2017-04-11 | David Gordon Bermudes | Modified bacteria having improved pharmacokinetics and tumor colonization enhancing antitumor activity |
WO2016088376A1 (en) * | 2014-12-03 | 2016-06-09 | 株式会社アネロファーマ・サイエンス | Coexpression plasmid |
CN107208108B (en) | 2015-01-19 | 2019-05-17 | 国立大学法人信州大学 | Therapeutic agent for ischemic diseases |
US10076556B2 (en) | 2015-01-29 | 2018-09-18 | Oxyrase, Inc. | Methods for inhibiting tumor growth |
US10676723B2 (en) | 2015-05-11 | 2020-06-09 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
US11180535B1 (en) | 2016-12-07 | 2021-11-23 | David Gordon Bermudes | Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria |
US11471497B1 (en) | 2019-03-13 | 2022-10-18 | David Gordon Bermudes | Copper chelation therapeutics |
US10973908B1 (en) | 2020-05-14 | 2021-04-13 | David Gordon Bermudes | Expression of SARS-CoV-2 spike protein receptor binding domain in attenuated salmonella as a vaccine |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2002A (en) * | 1841-03-12 | Tor and planter for plowing | ||
US4486407A (en) * | 1983-02-28 | 1984-12-04 | Fumiaki Taguchi | Method for enhancing production of interferon |
JPH05174434A (en) * | 1991-12-26 | 1993-07-13 | Sharp Corp | Magneto-optical recording disk |
US6984513B2 (en) * | 1994-03-03 | 2006-01-10 | The Board Of Trustees Of The Leland Stanford Junior University | Anaerobe targeted enzyme-mediated prodrug therapy |
US6416754B1 (en) * | 1994-03-03 | 2002-07-09 | The Board Of Trustees Of The Leland Stanford Junior University | Anaerobe targeted enzyme-mediated prodrug therapy |
IT1270123B (en) | 1994-10-05 | 1997-04-28 | Dompe Spa | PHARMACEUTICAL COMPOSITIONS CONTAINING ENGINEERED MICROORGANISMS AND THEIR USE FOR THERAPY |
US6190657B1 (en) * | 1995-06-07 | 2001-02-20 | Yale University | Vectors for the diagnosis and treatment of solid tumors including melanoma |
FR2746016B1 (en) * | 1996-03-15 | 1998-04-17 | COMBINATIONS OF ENZYMES FOR THE DESTRUCTION OF PROLIFERATIVE CELLS | |
JPH10111517A (en) | 1996-10-08 | 1998-04-28 | Omron Corp | Liquid crystal display device |
CN1253551C (en) * | 1997-09-10 | 2006-04-26 | 维昂药品公司 | Genetically modified tumor-targeted bacteria with reduced virulence |
US6080849A (en) * | 1997-09-10 | 2000-06-27 | Vion Pharmaceuticals, Inc. | Genetically modified tumor-targeted bacteria with reduced virulence |
ID29150A (en) * | 1999-01-15 | 2001-08-02 | Entpr Ireland Cs | USE OF LACTOBACILLUS SALIVARIUS |
WO2001014579A2 (en) * | 1999-08-26 | 2001-03-01 | Vion Pharmaceuticals, Inc. | Compositions and methods for delivery of an agent using attenuated salmonella containing phage |
US6962696B1 (en) * | 1999-10-04 | 2005-11-08 | Vion Pharmaceuticals Inc. | Compositions and methods for tumor-targeted delivery of effector molecules |
-
2001
- 2001-03-26 CA CA2342040A patent/CA2342040C/en not_active Expired - Lifetime
- 2001-03-26 US US09/816,391 patent/US20020054865A1/en not_active Abandoned
-
2004
- 2004-02-23 US US10/782,899 patent/US7740835B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CA2342040C (en) | 2012-07-10 |
US7740835B2 (en) | 2010-06-22 |
US20020054865A1 (en) | 2002-05-09 |
US20050025745A1 (en) | 2005-02-03 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKEX | Expiry |
Effective date: 20210326 |