EP1066061A1 - Use of scatter factor to enhance angiogenesis - Google Patents
Use of scatter factor to enhance angiogenesisInfo
- Publication number
- EP1066061A1 EP1066061A1 EP99914117A EP99914117A EP1066061A1 EP 1066061 A1 EP1066061 A1 EP 1066061A1 EP 99914117 A EP99914117 A EP 99914117A EP 99914117 A EP99914117 A EP 99914117A EP 1066061 A1 EP1066061 A1 EP 1066061A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- scatter factor
- tissue
- ischemia
- nucleic acid
- disease
- 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.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1833—Hepatocyte growth factor; Scatter factor; Tumor cytotoxic factor II
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- 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
Definitions
- This invention relates to a method of enhancing wound healing and to a method of enhancing organ transplantation comprising the administration of scatter factor to promote angiogenesis .
- Scatter factor has previously been described as a cytokine which is secreted by fibroblasts (see Stoker et al., J. Cell Sci . , Vol. 77, pp. 209-223 (1985) and Stoker et al., Nature (London), Vol. 327, pp. 238-242 (1987)) and by vascular smooth muscle cells (see Rosen et al . , In Vi tro Cell Dev. Biol . , Vol. 25, pp. 163-173 (1989)). Scatter factor has been shown to disperse cohesive epithelial colonies and stimulate cell motility.
- HGF hepatocyte growth factor
- HGF Scatter factor
- angiogenesis refers to the formation of blood vessels. Specifically, angiogenesis is a multistep process in which endothelial cells focally degrade and invade through their own - 3 - basement membrane, migrate through interstitial stroma toward an angiogenic stimulus, proliferate proximal to the migrating tip, organize into blood vessels, and reattach to newly synthesized basement membrane (see Folkman et al . , Adv. Cancer Res . , Vol. 43, pp. 175-203 (1985)). These processes are controlled by soluble factors and by the extracellular matrix (see Ingber et al . , Cell , Vol. 58, pp. 803-805 (1985) ) .
- proteases such as plasminogen activators (the endothelial secretion of which is induced by scatter factor) are required during the early stages of angiogenesis, and since endothelial cell migration, proliferation and capillary tube formation occur during angiogenesis, the inventors hypothesized that scatter factor might enhance angiogenic activity in vivo . In addition, it is desirable to enhance angiogenic activity so that wound healing and organ transplantation can be enhanced.
- This invention is directed to a method of promoting angiogenesis by administration of scatter factor.
- the promotion of angiogenesis can be used for promoting wound healing and treating various conditions where the - 4 - promotion of angiogenesis is desirable, including, but not limited to, ischemia.
- Figures 1A-1C show the effects of SF/HGF gene transfer on rat myocardium.
- Figure 1A shows immunostaining with monoclonal antibodies directed against human SF/HGF in myocardial tissue 5 days following infarction and gene transfection.
- Figure IB and 1C show myocardial tissue from SF/HGF-treated and control animals, respectively, treated with anti -endothelial CD-34 antibody and stained using peroxidase-based immunohistochemistry .
- the present invention is directed to a method of promoting angiogenesis in a tissue or subject by administering scatter factor to a subject in need of angiogenesis promotion.
- the method provided by the present invention involves the administration of scatter factor to promote angiogenesis in various tissues to promote wound healing,
- the administration of scatter factor may be effected by administration of the protein itself or administration - 5 - of a nucleic acid encoding scatter factor by the use of standard DNA techniques .
- Scatter factor protein may be administered to a tissue or subject topically or by intravenous, intramuscular, intradermal, subcutaneous or intraperitoneal injection. Scatter factor protein is administered in amounts sufficient to promote angiogenesis in a subject, which is in the amount of about .1-1000 ng/kg body weight .
- Scatter factor protein may be administered as the wild type scatter factor protein, or analogues thereof, and may be produced synthetically or recombinantly, or may be isolated from native cells.
- “analogue” means functional variants of the wild type protein, and includes scatter factor protein isolated from mammalian sources other than human, such as mouse, as well as functional variants thereof.
- a nucleic acid sequence encoding scatter factor administered to a mammal may be genomic DNA or cDNA.
- the nucleic acid sequence may be administered using a number of procedures known to one skilled in the art, such as electroporation, DEAE Dextran, monocationic liposome fusion, polycationic liposome fusion, protoplast fusion, DNA coated microprojectile bombardment, by creation of an in vivo electrical field, injection with recombinant replication-defective viruses, homologous recombination, and naked DNA transfer. It is to be appreciated by one skilled in the art that any of the above methods of DNA transfer may be combined.
- a nucleic acid encoding scatter factor may also be administered to a mammal using gene therapy, i.e.
- a recombinant vector containing a nucleic acid sequence encoding scatter factor may be administered to a mammal using any number of procedures known to one skilled in the art, including, but not limited to, electroporation, DEAE Dextran transfection, calcium phosphate transfection, cationic liposome fusion, protoplast fusion, by creation of an in vivo electrical field, DNA coated microprojectile bombardment, injection with recombinant replication- defective viruses, homologous recombination, gene therapy, and naked DNA transfer.
- a cell such as a stem cell or a tumor cell which expresses scatter factor introduced therein through viral transduction, homologous recombination, or transfection is also provided by the present invention. This cell may then be administered to a subject to promote angiogenesis.
- the recombinant vector may comprise a nucleic acid of or corresponding to at least a portion of the genome of a virus, where this portion is capable of directing the expression of a nucleic sequence encoding scatter factor, operably linked to the viral nucleic acid and capable of being expressed as a functional gene product in the subject mammal.
- the recombinant vectors may be derived from a variety of viral nucleic acids known to one skilled in the art, e.g. the genomes of HSV, adenovirus, adeno- associated virus, Semiliki Forest virus, vaccinia virus, and other viruses, including RNA and DNA viruses. - 7 -
- the recombinant vectors may also contain a nucleotide sequence encoding suitable regulatory elements so as to effect expression of the vector construct in a suitable host cell.
- expression refers to the ability of the vector to transcribe the inserted DNA sequence into mRNA so that synthesis of the protein encoded by the inserted nucleic acid can occur.
- enhancers and promoters are suitable for use in the constructs of the invention, and that the constructs will contain the necessary start, termination, and control sequences for proper transcription and processing of the nucleic acid sequence encoding scatter factor when the recombinant vector construct is introduced into a mammal.
- Vectors suitable for the expression of the nucleic sequence encoding scatter factor are well known to one skilled in the art and include pMEX, pRSX24 (provided by Dr. George Vande oude, Frederick Cancer Center, Frederick, Maryland) , pSV2neo (Clonetech) , pET-3d (Novagen) , pProEx-1 (Life Technologies) , pFastBac 1 (Life Technologies).
- Suitable promoters include, but are not limited to, constitutive promoters, tissue specific promoters, and inducible promoters.
- Expression of the nucleic acid sequence encoding scatter factor may be controlled and affected by the particular vector into which the nucleic acid sequence has been introduced.
- Some eukaryotic vectors have been engineered so that they are capable of expressing inserted nucleic acids to high levels within the target cell. Such vectors utilize one of a number of powerful promoters to direct the high level of expression.
- Eukaryotic vectors use promoter-enhancer sequences of viral genes, especially those of tumor viruses.
- a particular embodiment of the invention provides for regulation of expression of the nucleic acid sequence encoding scatter factor using inducible promoters.
- inducible promoters include, but are not limited to, metallothionine promoters and mouse mammary tumor virus promoters.
- promoters and enhancers effective for use in the recombinant vectors include, but are not limited to, CMV (cytomegalovirus) , SV40 (simian virus 40) , HSV (herpes simplex virus) , EBV (epstein-barr virus) , retroviral, adenoviral promoters and enhancers, and tumor cell specific promoters and enhancers.
- CMV cytomegalovirus
- SV40 simian virus 40
- HSV herpes simplex virus
- EBV epstein-barr virus
- retroviral adenoviral promoters and enhancers
- tumor cell specific promoters and enhancers include, but are not limited to, CMV (cytomegalovirus) , SV40 (simian virus 40) , HSV (herpes simplex virus) , EBV (epstein-barr virus) , retroviral, adenoviral promoters and enhancers, and tumor cell specific promote
- scatter factor may be administered in combination with a growth factor to promote angiogenesis, including, but not limited to TGF- ⁇ , FGF and PDGF .
- Scatter factor in the form of a protein, nucleic acid, or a recombinant vector containing nucleic acid encoding scatter factor, may be administered to a subject prior to, simultaneously with or subsequent to administration of a growth factor.
- a recombinant vector containing nucleic acid encoding scatter factor may be combined with a sterile aqueous solution which is preferably isotonic with the blood of the recipient .
- Such formulations may be prepared by suspending the recombinant vector in water containing physiologically compatible substances such as sodium chloride, glycine, and the like, and having buffered pH compatible with physiological conditions to produce an aqueous solution, and rendering such solution sterile.
- physiologically compatible substances such as sodium chloride, glycine, and the like
- the recombinant vector is combined with a 20-25% sucrose in saline solution in preparation for introduction into a mammal.
- nucleic acid encoding scatter factor or nucleic acid encoding scatter factor contained in a vector are administered in amounts sufficient to promote angiogenesis in a subject.
- the exact dosage will depend on such factors as the purpose of administration, the mode of administration, and the efficacy of the composition, as well as the individual pharmacokinetic parameters of the subject.
- Such therapies may be - 10 - administered as often as necessary and for the period of time as judged necessary by one of skill in the art.
- Non-limiting examples of tissues into which nucleic acid encoding scatter factor may be introduced to promote angiogensis include fibrous, endothelial, epithelial, vesicular, cardiac, cerebrovascular, muscular, vascular, transplanted, and wounded tissues.
- Transplanted tissues are, for example, heart, kidney, lung, liver and ocular tissues.
- the tissues into which nucleic acid encoding scatter factor may be introduced to promote angiogensis include those associated with diseases or conditions selected from the group consisting of ischemia, circulatory disorders, vascular disorders, myocardial ischemic disorders, myocardial disease, pericardial disease or congenital heart disease.
- Non-limiting examples of ischemia are myocardial ischemia, cerebrovascular ischemia and veno- occlusive disorder.
- An example of myocardial ischemia is coronary artery disease.
- scatter factor is used to enhance wound healing, organ regeneration, and organ transplantation, including the transplantation of artificial organs.
- scatter factor can be used to accelerate endothelial cell coverage of vascular grafts in order to prevent graft failure due to reocclusion, and to enhance skin grafting.
- antibodies to scatter factor can be used to treat tumors and to prevent tumor growth.
- the plasmid pRSX24 was constructed by ligating full-length 2.3 kb SF cDNA into the BamHI-Kpnl site of the pMEX vector, and was provided by Dr. George Vande Woude (Frederick Cancer Center, Frederick, MD) . Expression of Scatter Factor in normal ischemic tissue . In order to ascertain potential expression of HGF using the plasmid PRSX24 on normal ischemic tissue, Sprague-Dawley rats weighing 210-300 were anesthetized, intubated and placed on a positive-pressure respirator.
- the left coronary artery was ligated 3-4 millimeters from its origin to produce myocardial infarction, and at the same time, the apices of the heart were injected with 40 micrograms of the PRSX24 (HSF) plasmid.
- HSF PRSX24
- FIG. 1A shows immunostaining with monoclonal antibodies directed against - 12 - human SF/HGF in myocardial tissue 5 days following infarction and gene transfection; staining patterns were significantly more dense in group treated with SF/HGF plasmid than controls (not shown) .
- Figures IB and 1C show myocardial tissue from SF/HGF-treated and control animals, respectively, treated with anti-endothelial CD-34 antibody (Becton Dickenson) and stained using peroxidase-based immunohistochemistry (Ventana Medical Systems) ; increased vascularity is seen in the myocardium of SF/HGF-treated animals 20 days following surgery and transfection.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Vascular Medicine (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US4881398A | 1998-03-26 | 1998-03-26 | |
US48813 | 1998-03-26 | ||
PCT/US1999/006452 WO1999048537A1 (en) | 1998-03-26 | 1999-03-26 | Use of scatter factor to enhance angiogenesis |
Publications (2)
Publication Number | Publication Date |
---|---|
EP1066061A1 true EP1066061A1 (en) | 2001-01-10 |
EP1066061A4 EP1066061A4 (en) | 2003-01-08 |
Family
ID=21956589
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP99914117A Withdrawn EP1066061A4 (en) | 1998-03-26 | 1999-03-26 | Use of scatter factor to enhance angiogenesis |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP1066061A4 (en) |
JP (1) | JP2002507584A (en) |
AU (1) | AU3202999A (en) |
CA (1) | CA2326053A1 (en) |
MX (1) | MXPA00009440A (en) |
WO (1) | WO1999048537A1 (en) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1114862A3 (en) * | 1999-11-17 | 2003-08-06 | Switch Biotech Aktiengesellschaft | Use of polyeptides or their encoding nucleic acids for the diagnosis or treatment of skin diseases and their use in indentifying pharmacologically acitve substances |
EP1176200A3 (en) * | 2000-06-20 | 2005-01-12 | Switch Biotech Aktiengesellschaft | Use of polyeptides or their encoding nucleic acids for the diagnosis or treatment of skin diseases or wound healing and their use in indentifying pharmacologically acitve substances |
EP1391214A4 (en) * | 2001-05-09 | 2006-05-17 | Anges Mg Inc | Gene transfer of angiogenic factor for skin disease |
TWI395756B (en) | 2003-07-18 | 2013-05-11 | Amgen Inc | Specific binding agents to hepatocyte growth factor |
FI20065514A0 (en) * | 2006-08-16 | 2006-08-16 | Licentia Oy | Activated fibroblasts for the treatment of tissue damage |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997012629A1 (en) * | 1995-10-05 | 1997-04-10 | Genentech, Inc. | Improved angiogenesis using hepatocyte growth factor |
US5652225A (en) * | 1994-10-04 | 1997-07-29 | St. Elizabeth's Medical Center Of Boston, Inc. | Methods and products for nucleic acid delivery |
EP0847757A1 (en) * | 1995-08-29 | 1998-06-17 | Sumitomo Pharmaceuticals Company, Limited | Medicine comprising hgf gene |
-
1999
- 1999-03-26 AU AU32029/99A patent/AU3202999A/en not_active Abandoned
- 1999-03-26 JP JP2000537583A patent/JP2002507584A/en active Pending
- 1999-03-26 CA CA002326053A patent/CA2326053A1/en not_active Abandoned
- 1999-03-26 EP EP99914117A patent/EP1066061A4/en not_active Withdrawn
- 1999-03-26 MX MXPA00009440A patent/MXPA00009440A/en unknown
- 1999-03-26 WO PCT/US1999/006452 patent/WO1999048537A1/en not_active Application Discontinuation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5652225A (en) * | 1994-10-04 | 1997-07-29 | St. Elizabeth's Medical Center Of Boston, Inc. | Methods and products for nucleic acid delivery |
EP0847757A1 (en) * | 1995-08-29 | 1998-06-17 | Sumitomo Pharmaceuticals Company, Limited | Medicine comprising hgf gene |
WO1997012629A1 (en) * | 1995-10-05 | 1997-04-10 | Genentech, Inc. | Improved angiogenesis using hepatocyte growth factor |
Non-Patent Citations (11)
Title |
---|
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1994 WATANABE SUMIO ET AL: "Hepatocyte growth factor accelerates the wound repair of cultured gastric mucosal cells." Database accession no. PREV199497222079 XP002219961 & BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 199, no. 3, 1994, pages 1453-1460, ISSN: 0006-291X * |
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1995 VAN BELLE ERIC ET AL: "Scatter factor stimulates angiogenesis in a rabbit model of hindlimb ischemia." Database accession no. PREV199698586061 XP002219968 & CIRCULATION, vol. 92, no. 8 SUPPL., 1995, page I748 68th Scientific Session of the American Heart Association;Anaheim, California, USA; November 13-16, 1995 ISSN: 0009-7322 * |
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1996 HAYASHI SHIN-ISHIRO ET AL: "Hypoxia down-regulated a novel angiogenic growth factor, hepatocyte growth factor (HGF) in human vascular cells, and transfection of HGF gene rescued endothelial cell death induced by hypoxia." Database accession no. PREV199799303954 XP002219967 & CIRCULATION, vol. 94, no. 8 SUPPL., 1996, page I463 69th Scientific Sessions of the American Heart Association;New Orleans, Louisiana, USA; November 10-13, 1996 ISSN: 0009-7322 * |
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1996 KATO KAZUYA ET AL: "Effect of hepatocyte growth factor on the proliferation of intrasplenically transplanted hepatocytes in rats." Database accession no. PREV199699010900 XP002219959 & BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 222, no. 1, 1996, pages 101-106, ISSN: 0006-291X * |
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1997 LATERRA JOHN ET AL: "Scatter factor/hepatocyte growth factor gene transfer enhances glioma growth and angiogenesis in vivo." Database accession no. PREV199799551720 XP002219957 & LABORATORY INVESTIGATION, vol. 76, no. 4, 1997, pages 565-577, ISSN: 0023-6837 * |
DATABASE MEDLINE [Online] BUSSOLINO ET AL: "Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth" Database accession no. NLM1383237 XP002219958 & THE JOURNAL OF CELL BIOLOGY, vol. 119, 1992, pages 629-641, * |
DATABASE MEDLINE [Online] KIM ET AL: " Enhanced survival of transgenic hepatocytes expressing hepatocyte growth factor in hepatocyte tissue engineering" Database accession no. NLM9123555 XP002219960 & TRANSPLANTATION PROCEEDINGS, vol. 29, 1997, pages 858-860, * |
GRANT D S ET AL: "SCATTER FACTOR INDUCES BLOOD VESSEL FORMATION IN VIVO" PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE. WASHINGTON, US, vol. 90, March 1993 (1993-03), pages 1937-1941, XP002935422 ISSN: 0027-8424 * |
ROSEN E M ET AL: "SCATTER FACTOR AND ANGIOGENESIS" ADVANCES IN CANCER RESEARCH, ACADEMIC PRESS, LONDON, GB, vol. 67, 1995, pages 257-279, XP000615858 ISSN: 0065-230X * |
See also references of WO9948537A1 * |
UEDA H ET AL: "IN VIVO GENE TRANSFECTION OF HEPATOCYTE GROWTH FACTOR ATTENUATES ISCHEMIA-REPERFUSION INJURY IN THE HEART: EVIDENCE FOR A ROLE OF HGF IN ENDOGENOUS MYOCARDIAL PROTECTION" CIRCULATION, AMERICAN HEART ASSOCIATION, DALLAS, TX, US, vol. 96, no. 8, 1997, page 1619 XP002936330 ISSN: 0009-7322 * |
Also Published As
Publication number | Publication date |
---|---|
CA2326053A1 (en) | 1999-09-30 |
MXPA00009440A (en) | 2003-04-22 |
AU3202999A (en) | 1999-10-18 |
EP1066061A4 (en) | 2003-01-08 |
JP2002507584A (en) | 2002-03-12 |
WO1999048537A1 (en) | 1999-09-30 |
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