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

Signal tnf dans les traitements du virus du myxome Download PDF

Info

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
Authority
WO
WIPO (PCT)
Prior art keywords
necrosis factor
tumor necrosis
subject
myxoma virus
human
Prior art date
Application number
PCT/US2007/070216
Other languages
English (en)
Other versions
WO2007143545A3 (fr
Inventor
Grant Mcfadden
Fuan Wang
Michael Scot Roberts
Original Assignee
Robarts Research Institute
Wellstat Biologics Corporation
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 Corporation filed Critical Robarts Research Institute
Publication of WO2007143545A2 publication Critical patent/WO2007143545A2/fr
Publication of WO2007143545A3 publication Critical patent/WO2007143545A3/fr

Links

Classifications

    • 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.

Landscapes

  • 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 Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (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 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 WO2007143545A2 (fr) 2006-06-01 2007-06-01 Signal tnf dans les traitements du virus du myxome

Country Status (1)

Country Link
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

Citations (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

Patent Citations (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

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
MCFADDEN ET AL.: 'Interruption of Cytokine Networks by Poxviruses: Lessons from Myxoma Virus' JOURNAL OF LEUKOCYTE BIOLOGY May 1995, pages 731 - 738 *
SCHREIBER ET AL.: 'Distinct Domains of M-T2, the Myxoma Virus Tumor Necrosis Factor (TNF) Receptor Homolog, Mediate Extracellular TNF Binding and Intracellular Apoptosis Inhibition' JOURNAL OF VIROLOGY vol. 71, March 1997, pages 2171 - 2181 *
SCHREIBER ET AL.: 'Myxoma Virus T2 Protein, a Tumor Necrosis Factor (TNF) receptor Homolog, is Secreted as a Monomer and Dimer That Each Bind Rabbit TNF-alpha, but the Dimer is a More Potent TNF Inhibitor' JOURNAL OF BIOLOGICAL CHEMISTRY vol. 271, June 1996, pages 13333 - 13341 *

Cited By (10)

* 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
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
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
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
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
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

Also Published As

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

Similar Documents

Publication Publication Date Title
Channappanavar et al. IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes
Paludan et al. Innate immunological pathways in COVID-19 pathogenesis
Mueller et al. Why does COVID-19 disproportionately affect older people?
Liu et al. A class of viral inducer of degradation of the necroptosis adaptor RIPK3 regulates virus-induced inflammation
Aarreberg et al. Interleukin-1β signaling in dendritic cells induces antiviral interferon responses
Kumar et al. Inflammasome adaptor protein Apoptosis-associated speck-like protein containing CARD (ASC) is critical for the immune response and survival in west Nile virus encephalitis
Lehmann et al. CCL2 expression is mediated by type I IFN receptor and recruits NK and T cells to the lung during MVA infection
Khaitov et al. Respiratory virus induction of alpha‐, beta‐and lambda‐interferons in bronchial epithelial cells and peripheral blood mononuclear cells
Klein et al. Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus encephalitis
Phares et al. CD4 T cells promote CD8 T cell immunity at the priming and effector site during viral encephalitis
Fink et al. Early type I interferon‐mediated signals on B cells specifically enhance antiviral humoral responses
Vijay et al. Virus-induced inflammasome activation is suppressed by prostaglandin D2/DP1 signaling
McCaffrey et al. The host response to adenovirus, helper-dependent adenovirus, and adeno-associated virus in mouse liver
Borkham-Kamphorst et al. Antisense strategy against PDGF B-chain proves effective in preventing experimental liver fibrogenesis
Hwang et al. Alpha/beta interferon (IFN-α/β) signaling in astrocytes mediates protection against viral encephalomyelitis and regulates IFN-γ-dependent responses
Friebe et al. Immunomodulatory effects of inactivated parapoxvirus ovis (ORF virus) on human peripheral immune cells: induction of cytokine secretion in monocytes and Th1-like cells
Lieskovska et al. Tick salivary cystatin sialostatin L2 suppresses IFN responses in mouse dendritic cells
Lehmann et al. Modified vaccinia virus ankara triggers chemotaxis of monocytes and early respiratory immigration of leukocytes by induction of CCL2 expression
Morrell et al. Beta interferon suppresses the development of experimental cerebral malaria
Monsuez et al. Cytokines in HIV-associated cardiomyopathy
Martorelli et al. A natural HIV p17 protein variant up‐regulates the LMP‐1 EBV oncoprotein and promotes the growth of EBV‐infected B‐lymphocytes: Implications for EBV‐driven lymphomagenesis in the HIV setting
Morrison et al. Complement receptor 3 promotes severe ross river virus-induced disease
Steain et al. Upregulation of CXCL10 in human dorsal root ganglia during experimental and natural varicella-zoster virus infection
Spel et al. Detection of viruses by inflammasomes
Rogers et al. IL-4/IL-13 polarization of macrophages enhances Ebola virus glycoprotein-dependent infection

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07798011

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase in:

Ref country code: DE

NENP Non-entry into the national phase in:

Ref country code: RU

122 Ep: pct application non-entry in european phase

Ref document number: 07798011

Country of ref document: EP

Kind code of ref document: A2