CA2274498A1 - Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease - Google Patents

Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease Download PDF

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Publication number
CA2274498A1
CA2274498A1 CA002274498A CA2274498A CA2274498A1 CA 2274498 A1 CA2274498 A1 CA 2274498A1 CA 002274498 A CA002274498 A CA 002274498A CA 2274498 A CA2274498 A CA 2274498A CA 2274498 A1 CA2274498 A1 CA 2274498A1
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CA
Canada
Prior art keywords
cells
accessory molecule
ligand
gene
pharmaceutical composition
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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
Application number
CA002274498A
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French (fr)
Other versions
CA2274498C (en
Inventor
Thomas J. Kipps
Sanjai Sharma
Mark Cantwell
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University of California
Original Assignee
University Of California
Thomas J. Kipps
Sanjai Sharma
Mark Cantwell
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Application filed by University Of California, Thomas J. Kipps, Sanjai Sharma, Mark Cantwell filed Critical University Of California
Priority to CA2707726A priority Critical patent/CA2707726C/en
Publication of CA2274498A1 publication Critical patent/CA2274498A1/en
Application granted granted Critical
Publication of CA2274498C publication Critical patent/CA2274498C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/48—Nerve growth factor [NGF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/525—Tumour necrosis factor [TNF]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/525—Tumour necrosis factor [TNF]
    • C07K14/5255—Lymphotoxin [LT]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • 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
    • C12N2799/00—Uses of viruses
    • C12N2799/02—Uses of viruses as vector
    • C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid

Abstract

This invention relates to genes which encode accessory molecule ligands and their use for immunomodulation, vaccination and treatments of various human diseases, including malignancies and autoimmune diseases. This invention also describes the use of accessory molecule ligands which are made up of various domains and subdomain portions of molecules derived from the tumor necrosis factor family. The chimeric molecules of this invention contain unique properties which lead to the stabilization of their activities and thus greater usefulness in the treatment of diseases. Vectors for expressing genes which encode the molecules of this invention are also discussed.

Claims (35)

1. A method of altering the immunoreactivity of human cells, which method comprises introducing a gene encoding an accessory molecule ligand into said cells so that said accessory molecule ligand is expressed on the surface of said cells, wherein said accessory molecule ligand has a greater stabilized activity relative to a corresponding native accessory molecule ligand.
2. The method of claim 1 wherein an accessory molecule to which the accessory molecule ligand can bind is also present on the surface of said cells.
3. The method of claim 1 wherein said human cells are neoplastic human cells.
4. The method in claim 1 wherein said accessory molecule ligand gene is present in a vector capable of transducing human cells.
5. The method of claim 1 wherein said accessory molecule ligand gene is present as part of a genetic vector.
6. The method of claim 1 wherein said accessory molecule ligand gene is operatively linked to a promoter region and a polyadenylation signal.
7. The method of claim 6 wherein said CD40 ligand gene is a murine CD40 ligand gene.
8. A human cell containing a gene therapy vector comprising a gene encoding an accessory molecule ligand which exhibits a greater stabilized activity in said human cells relative to a native accessory molecule ligand in said human cells.
9. The human cell of claim 8 wherein said cell is an antigen presenting cell.
10. The human cell of claim 8 wherein said human cell is a neoplastic cell.
11. The human cell of claim 8 wherein said cell is an accessory cell.
12. A pharmaceutical composition for vaccinating an animal against a predetermined organism comprising an immunogenic antigen capable of causing an immune response to said predetermined organism together with a vector containing a gene encoding an accessory molecule ligand, wherein said gene encoding said accessory molecule has a greater stabilized activity relative to a native accessory molecule ligand present in said vaccinated animal.
13. The pharmaceutical composition of claim 12 wherein said immunogenic antigen is encoded by genes present on a genetic vector.
14. The pharmaceutical composition of claim 12 wherein said predetermined organism is a virus, a bacteria, a fungus or a neoplastic cell.
15. A pharmaceutical composition for producing an immune response directed to a predetermined antigen upon administration to an animal, comprising: an antigen and a genetic vector containing a gene encoding an accessory molecule ligand gene, wherein said gene encoding said accessory molecule has a greater stability on the surface of cells relative to a native accessory molecule ligand present in said animal to generate said immune response.
16. A pharmaceutical composition for treating rheumatoid arthritis in a joint comprising a gene which encodes an accessory joint so that said accessory molecule ligand is expressed on the surface of said cells within the joint, and which ligand exhibits a greater stability on the surface of said cells relative to a native accessory molecule ligand present on the cells ef the afflicted patient.
17. The composition of claim 16 wherein said accessory molecule ligand gene is a murine Fas-ligand gene.
18. A pharmaceutical composition for infusion and treatment of a rheumatic arthritic joint, comprising: cells which have been transformed with a gene encoding an accessory molecule ligand that is expressed on the surface of said cells, wherein said ligand exhibits a greater stabilized activity relative to a native accessory molecule ligand present in cells of said joint.
19. A pharmaceutical composition which alters the immunoreactivity of animal cells, comprising a gene encoding an accessory molecule ligand, wherein said ligand has a greater stabilized activity relative to a native accessory molecule ligand present in said animal in which altered immunoreactivity is desired.
20. The pharmaceutical composition of claim 19, wherein said animal cells in which altered immunoreactivity is desired are human.
21. The pharmaceutical composition of claim 19, wherein said gene selected is a murine gene.
22. The pharmaceutical composition of any of claims 19-21, wherein said accessory molecule ligand gene is a CD40 ligand gene.
23. The pharmaceutical composition of any of claims 19-21, wherein said accessory molecule ligand gene is a FAS ligand gene.
24. A pharmaceutical composition for treating a neoplasia in a patient comprising cells that express a gene that encodes an accessory molecule ligand having a greater stability than a native accessory molecule ligand present in said patient, said accessory molecule ligand expressed on the surface of said cells thereby causing said cells to more actively participate in an immune reaction on injection of said cells in a tumor bed of said patient.
25. The pharmaceutical composition of any of claims 18, 19, or 24, wherein said cells are neoplastic cells.
26. The pharmaceutical composition of any of claims 18, 19, or 24, wherein said cells are antigen presenting cells.
27. The pharmaceutical composition of any of claims 18, 19, or 24, wherein said cells are accessory cells.
28. The method of claim 3, wherein said cells are leukemic cells.
29. The method of claim 28, wherein said leukemic cells are chronic lymphocytic (CLL), chronic myelogenous (CML), myelomonocytic (MML), acute lymphocytic (ALL) and Non-Hodgkins lymphoma leukemias.
30. The pharmaceutical composition of claim 25, wherein said cells are leukemic cells.
31. The pharmaceutical composition of claim 30, wherein said leukemic cells are chronic lymphocytic (CLL), chronic myelogenous (CML), myelomonocytic (MML), acute lymphocytic (ALL) and Non-Hodgkins lymphoma leukemias.
32. The pharmaceutical composition of claims 12 or 15, wherein said vector containing said gene encoding said antigen and said vector containing said gene encoding said accessory molecule ligand are the same vector.
33. The pharmaceutical composition of claim 18, wherein said ligand encoded by said gene is a Fas ligand.
34. The pharmaceutical composition of claim 33, wherein said Fas ligand is a murine ligand.
35. Use of a gene encoding an accessory molecule ligand for preparing any of the pharmaceutical compositions of claims 12, 13, 14, 15, 17, 18, 19-27, and 30-34 for altering the immunoreactivity of animal including human cells, said pharmaceutical composition optionally comprising an immunogenic antigen and/or a pharmaceutically acceptable carrier or diluent.
CA2274498A 1996-12-09 1997-12-08 Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease Expired - Fee Related CA2274498C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2707726A CA2707726C (en) 1996-12-09 1997-12-08 Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US3214596P 1996-12-09 1996-12-09
US60/032,145 1996-12-09
US08/982,272 US7070771B1 (en) 1996-12-09 1997-12-01 Methods of expressing chimeric mouse and human CD40 ligand in human CD40+ cells
US08/982,272 1997-12-01
PCT/US1997/022740 WO1998026061A2 (en) 1996-12-09 1997-12-08 Expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease

Related Child Applications (1)

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CA2707726A Division CA2707726C (en) 1996-12-09 1997-12-08 Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease

Publications (2)

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CA2274498A1 true CA2274498A1 (en) 1998-06-18
CA2274498C CA2274498C (en) 2010-06-29

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US (3) US7070771B1 (en)
EP (4) EP1806360A3 (en)
JP (1) JP4015201B2 (en)
CN (1) CN1221662C (en)
AT (2) ATE420956T1 (en)
AU (1) AU5795798A (en)
BR (1) BR9714004A (en)
CA (2) CA2707726C (en)
DE (1) DE69739220D1 (en)
DK (1) DK0948614T3 (en)
ES (1) ES2321246T3 (en)
IL (3) IL130247A0 (en)
NO (2) NO327411B1 (en)
NZ (1) NZ336092A (en)
PT (1) PT948614E (en)
WO (1) WO1998026061A2 (en)

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NO992756L (en) 1999-08-09
BR9714004A (en) 2000-05-02
US7906638B2 (en) 2011-03-15
ES2321246T3 (en) 2009-06-03
JP4015201B2 (en) 2007-11-28
CN1246892A (en) 2000-03-08
EP1806360A2 (en) 2007-07-11
EP2145958B1 (en) 2012-02-29
NO331434B1 (en) 2011-12-27
PT948614E (en) 2009-04-20
EP0948614B1 (en) 2009-01-14
NZ336092A (en) 2001-09-28
IL178306A0 (en) 2007-02-11
US7070771B1 (en) 2006-07-04
JP2001505782A (en) 2001-05-08
CN1221662C (en) 2005-10-05
WO1998026061A3 (en) 1998-11-19
EP2145958A1 (en) 2010-01-20
CA2707726A1 (en) 1998-06-18
US20100267129A1 (en) 2010-10-21
WO1998026061A2 (en) 1998-06-18
EP0948614A2 (en) 1999-10-13
AU5795798A (en) 1998-07-03
US7524944B2 (en) 2009-04-28
US20060183199A1 (en) 2006-08-17
CA2707726C (en) 2013-10-22
EP2287309A1 (en) 2011-02-23
NO327411B1 (en) 2009-06-22
CA2274498C (en) 2010-06-29
DK0948614T3 (en) 2009-05-11
NO20074906L (en) 1999-08-09
DE69739220D1 (en) 2009-03-05
IL130247A0 (en) 2000-06-01
ATE420956T1 (en) 2009-01-15
ATE547524T1 (en) 2012-03-15
EP1806360A3 (en) 2007-12-12
IL130247A (en) 2008-03-20
NO992756D0 (en) 1999-06-07

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