WO2007143545A2 - Signal tnf dans les traitements du virus du myxome - Google Patents

Signal tnf dans les traitements du virus du myxome Download PDF

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Publication number
WO2007143545A2
WO2007143545A2 PCT/US2007/070216 US2007070216W WO2007143545A2 WO 2007143545 A2 WO2007143545 A2 WO 2007143545A2 US 2007070216 W US2007070216 W US 2007070216W WO 2007143545 A2 WO2007143545 A2 WO 2007143545A2
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WO
WIPO (PCT)
Prior art keywords
necrosis factor
tumor necrosis
subject
myxoma virus
human
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.)
Ceased
Application number
PCT/US2007/070216
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English (en)
Other versions
WO2007143545A3 (fr
Inventor
Grant Mcfadden
Fuan Wang
Michael Scot Roberts
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Robarts Research Institute
Wellstat Biologics Corp
Original Assignee
Robarts Research Institute
Wellstat Biologics Corp
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Robarts Research Institute, Wellstat Biologics Corp filed Critical Robarts Research Institute
Publication of WO2007143545A2 publication Critical patent/WO2007143545A2/fr
Publication of WO2007143545A3 publication Critical patent/WO2007143545A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

Definitions

  • Myxoma virus is a rabbit-specific poxvirus. In other words, MV only infects rabbits in natural settings.
  • Previous studies have shown that the species barrier for MV in mice is maintained by inteferon (IFN) signaling. While MV is capable of infecting humans, MV cannot cause disease in humans even if it is injected on purpose. However, the molecular mechanism underlying the species restriction in humans was not known.
  • TNF has been shown to have direct antiviral activity against some DNA and RNA viruses (Mestan, et al, Nature (October 1986) 323:816-819; Wong and Goeddel, Nature (October 1986) 323:819-822), but the antiviral activity of TNF against myxoma in human cells was not previously known.
  • This invention is based on the identification of the TNF ⁇ -NF ⁇ B signaling cascade as the major component for the myxoma virus (MV) species barrier in humans.
  • the species barrier for myxoma virus in humans is TNF ⁇ -NF ⁇ B dependent.
  • This invention provides a method for identifying cells susceptible to infection with a myxoma virus, comprising assaying a test cell for responsiveness to tumor necrosis factor (TNF), wherein a cell that is deficient in TNF responsiveness is identified as likely being susceptible to myxoma virus infection.
  • TNF tumor necrosis factor
  • any kind of cell can be tested.
  • the cell is a human cell, for example a human cancer cell.
  • the TNF is TNF-alpha.
  • This invention provides a method of treating a human subject having a myxoma virus infection, comprising administering an activator of tumor necrosis factor receptor to the subject in an amount effective to treat the subject.
  • the TNF receptor activator is TNF, more preferably TNF-alpha.
  • Other activators can also be used, such as agonist antibodies and synthentic peptides Activation of the TNF receptor leads to nuclear translocation of the transcription factor NF-kB.
  • Other agents capable of causing the nuclear translocation of NF-kB can be used in a manner analogous to the use of TNF.
  • These agents include, but are not limited to, Fas ligand, and agonists of Toll-like receptors (TLRs).
  • TLRs Toll-like receptors
  • This invention provides a method of treating a human subject having cancer, comprising administering to the subject a MT-2 deficient myxoma virus in an amount effective to treat the subject.
  • Myxoma and other viruses have evolved mechanisms to antagonize TNF signaling in a species-specific (natural host) manner, leading in part to the manifestation of the natural tropism.
  • This antagonism is not required in cells that are, in and of themselves, defective in TNF response, such as human tumor cells, and therefore the virus tropism is extended to these types of cells.
  • This antagonism is the myxoma M-T2 viral protein, which can bind to and sequester TNF ligand. Because tumor cells can become TNF-resistant, these viruses may grow and kill neoplastic cells from a non-natural host, the M-T2 viral protein is dispensable for growth in human tumor cells.
  • This invention provides a method of treating a human subject having cancer, comprising administering to the subject a myxoma virus that expresses tumor necrosis factor in cells of the subject.
  • the expressed tumor necrosis factor is human tumor necrosis factor, preferably tumor necrosis factor-alpha.
  • the myxoma virus is MT-2 deficient.
  • FIG. 1 Viral replication efficiency of the various vMyx-hrKOs and controls in human glioma cell lines.
  • Figure 3. Secreted early and late viral gene expression indicates that some of the vMyx-hrKO are unable to transit from early to late gene expression.

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Pathology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

La présente invention concerne des cellules déficientes quant à la capacité de répondre au facteur de nécrose tumorale (TNF) et donc susceptibles d'être infectées par un virus du myxome. Les personnes infectées par le virus du myxome sont traitées au moyen d'un activateur des récepteurs du facteur de nécrose tumorale. Les virus du myxome déficients en MT-2 se révèlent utiles dans le traitement du cancer.
PCT/US2007/070216 2006-06-01 2007-06-01 Signal tnf dans les traitements du virus du myxome Ceased WO2007143545A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US81004506P 2006-06-01 2006-06-01
US60/810,045 2006-06-01

Publications (2)

Publication Number Publication Date
WO2007143545A2 true WO2007143545A2 (fr) 2007-12-13
WO2007143545A3 WO2007143545A3 (fr) 2008-01-31

Family

ID=38802244

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2007/070216 Ceased WO2007143545A2 (fr) 2006-06-01 2007-06-01 Signal tnf dans les traitements du virus du myxome

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WO (1) WO2007143545A2 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7582614B2 (en) 2003-03-07 2009-09-01 Robarts Research Institute Use of myxoma virus for the therapeutic treatment of cancer and chronic viral infection
US8512713B2 (en) 2006-06-01 2013-08-20 Robarts Research Institute Myxoma virus mutants for cancer treatment
WO2020014670A1 (fr) * 2018-07-13 2020-01-16 Arizona Board Of Regents On Behalf Of Arizona State University Méthodes de traitement du cancer avec un virus de myxome exprimant un tnf
WO2021072273A1 (fr) * 2019-10-10 2021-04-15 Arizona Board Of Regents On Behalf Of Arizona State University Virus oncolytique comprenant des transgènes immunomodulateurs et utilisations de celui-ci
US11117934B2 (en) 2019-09-02 2021-09-14 Arizona Board Of Regents On Behalf Of Arizona State University Oncolytic virus platform to treat cancers with myxoma virus

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5464938A (en) * 1990-04-09 1995-11-07 Immunex Corporation Isolated viral protein TNF antagonists

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7582614B2 (en) 2003-03-07 2009-09-01 Robarts Research Institute Use of myxoma virus for the therapeutic treatment of cancer and chronic viral infection
US8227440B2 (en) 2003-03-07 2012-07-24 Robarts Research Institute Use of Myxoma virus for the therapeutic treatment of cancer and chronic viral infection
US8512713B2 (en) 2006-06-01 2013-08-20 Robarts Research Institute Myxoma virus mutants for cancer treatment
US9980994B2 (en) 2006-06-01 2018-05-29 Robarts Research Institute Myxoma virus mutants for cancer treatment
CN112996908A (zh) * 2018-07-13 2021-06-18 亚利桑那州立大学董事会 用表达tnf的粘液瘤病毒治疗癌症的方法
WO2020014670A1 (fr) * 2018-07-13 2020-01-16 Arizona Board Of Regents On Behalf Of Arizona State University Méthodes de traitement du cancer avec un virus de myxome exprimant un tnf
JP2021530249A (ja) * 2018-07-13 2021-11-11 アリゾナ ボード オブ リージェンツ オン ビハーフ オブ アリゾナ ステート ユニバーシティ Ｔｎｆ発現粘液腫ウイルスで癌を処置する方法
US12257278B2 (en) 2018-07-13 2025-03-25 Arizona Board Of Regents On Behalf Of Arizona State University Methods of treating cancer with TNF expressing myxoma virus
US11117934B2 (en) 2019-09-02 2021-09-14 Arizona Board Of Regents On Behalf Of Arizona State University Oncolytic virus platform to treat cancers with myxoma virus
CN114615988A (zh) * 2019-09-02 2022-06-10 亚利桑那州立大学董事会 用黏液瘤病毒治疗癌症的新型溶瘤病毒平台
US12331079B2 (en) 2019-09-02 2025-06-17 Arizona Board Of Regents On Behalf Of Arizona State University Oncolytic virus platform to treat cancers with myxoma virus
WO2021072273A1 (fr) * 2019-10-10 2021-04-15 Arizona Board Of Regents On Behalf Of Arizona State University Virus oncolytique comprenant des transgènes immunomodulateurs et utilisations de celui-ci
JP2023524920A (ja) * 2019-10-10 2023-06-14 アリゾナ・ボード・オブ・リージェンツ・オン・ビハーフ・オブ・アリゾナ・ステイト・ユニバーシティ 免疫調節導入遺伝子を含む腫瘍溶解性ウイルスおよびその使用

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Publication number Publication date
WO2007143545A3 (fr) 2008-01-31

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