WO2002002799A1 - Caracterisation d'une tumeur au cerveau - Google Patents

Caracterisation d'une tumeur au cerveau Download PDF

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Publication number
WO2002002799A1
WO2002002799A1 PCT/US2001/020615 US0120615W WO0202799A1 WO 2002002799 A1 WO2002002799 A1 WO 2002002799A1 US 0120615 W US0120615 W US 0120615W WO 0202799 A1 WO0202799 A1 WO 0202799A1
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WIPO (PCT)
Prior art keywords
receptor
sample
probe
brain tumor
grade
Prior art date
Application number
PCT/US2001/020615
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English (en)
Inventor
Waldemar Debinski
Original Assignee
The Penn State Research Foundation
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 The Penn State Research Foundation filed Critical The Penn State Research Foundation
Priority to AU2001268744A priority Critical patent/AU2001268744A1/en
Publication of WO2002002799A1 publication Critical patent/WO2002002799A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • 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
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
    • G01N33/6869—Interleukin
    • 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
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers

Definitions

  • the invention relates generally to the fields of pathology, medicine, and neuro- oncology. More particularly, the invention relates to the use of interleukin-13 (IL-13) binding
  • markers that occur on the plasma membrane or in a membrane receptor are particularly
  • Antibodies specific for tumor cell markers or ligands that bind specifically to a tumor cell receptor have been successfully used in diagnostics, including both the characterization
  • gliomas originate from glial tissue. Within this set of tumors are
  • Astrocytomas astrocytomas, brain stem gliomas, ependymomas, and oligodendogliomas.
  • Astrocytomas astrocytomas, brain stem gliomas, ependymomas, and oligodendogliomas.
  • astrocytes originate from star-shaped cells termed astrocytes; brain stem gliomas originate in the brain stem; ependymomas originate in the lining of the ventricles or spinal cord; and
  • oligodendrogliomas arise from myelin-producing cells. Brain tumors may also be of non-retrachloroatrinamic hormones.
  • non-glial tumors include medulloblastomas, meningiomas, Schwannomas,
  • craniopharyngiomas germ cell tumors, pineal region tumors, and secondary brain tumors.
  • grade a subjective categorization
  • the cells of a high grade tumor based on the microscopic appearance of its cells.
  • the cells of a high grade tumor based on the microscopic appearance of its cells.
  • grade IV have a more abnormal appearance than cells of a low grade (e.g., grade I)
  • Tumors are accorded a grade in order to provide an objective measurement of the seriousness of the disease in a patient with the tumor. Higher grade tumors are generally more malignant, while lower grade tumors are generally less malignant.
  • a grade I astrocytoma is less malignant than a grade II astrocytoma which is less
  • astrocytoma malignant than a grade III (or anaplastic) astrocytoma.
  • grade III or anaplastic
  • the most malignant astrocytoma is a grade IV astrocytoma also known as glioblastoma multiforme (GBM).
  • GBM glioblastoma multiforme
  • gliomas such as a gliomas
  • anaplastic astrocytomas and GBMs grow quickly and infiltrate surrounding tissue easily. In comparison, meningiomas grow much more slowly and with less infiltration. Because of these characteristics, anaplastic astrocytomas and GBMs typically demand more immediate and aggressive treatment than do meningiomas. Thus, methods for determining the type and grade of a brain tumor provide information that is often critical in selecting a course of treatment.
  • brain tumors are diagnosed by imaging.
  • brain tumors are diagnosed by imaging.
  • brain tumors are diagnosed by imaging.
  • brain tumors are diagnosed by imaging.
  • brain tumors are diagnosed by imaging.
  • the information provided by imaging is not limited to
  • the tumor may be biopsied so that a trained pathologist can microscopically examine a section of the biopsied sample to determine the type and grade of
  • Such a histopathological examination involves a certain degree of subjectivity on
  • the histopathological appearance of biopsy samples from the two grades of tumors may be difficult to differentiate and dependent on
  • low grade tumors may progress to high grade tumors.
  • the invention relates to the discovery that interleukin-13 (IL-13) binding can be used to characterize and distinguish among different types and grades of brain tumors.
  • IL-13 interleukin-13
  • GBMs glioblastoma multiformes
  • IL-13 binding was also assessed in other gliomas and in non-glial origin brain tumors. In these studies, oligodendrogliomas were found to express IL-13 binding sites when the
  • IL-13 receptor expression was not detected in the non-glial origin brain tumors examined, including secondary brain tumors (metastases) and those tumors of
  • the invention features a method of classifying a brain
  • This method includes the steps of: (a) providing a brain tumor sample; (b) quantifying the expression of an IL-13 receptor in the sample; and (c) correlating
  • the step of correlating the quantity of expression of the IL-13 receptor on the sample with a characteristic of the tumor can be performed by comparing the amount of IL-13 receptor expressed on the sample with the amount of IL-13 receptor expressed on a
  • the invention also features a method of distinguishing a higher-grade brain tumor
  • This method includes the steps of: providing a brain tumor sample; quantifying the expression of an IL-13 receptor in the sample; and correlating the
  • tumor is a higher grade brain tumor, and lower expression of the IL-13 receptor on the sample
  • Also within the invention is a method of analyzing the prognosis of subject with a
  • This method includes the steps of: (a) providing a sample of tissue isolated from
  • a brain tumor in the subject (b) quantifying the expression of an IL-13 receptor in the sample; and (c) correlating the quantity of expression of the IL-13 receptor on the sample with the prognosis of the tumor in the subject.
  • IL-13 receptor on the sample correlates with decreased likelihood of a poor prognosis.
  • the IL-13 receptor can be the restrictive form of IL-13
  • tumor sample can include surgically removing at least a portion of a brain tumor from a
  • the step of quantifying the expression of an IL-13 receptor in the sample can be any one of the following steps:
  • the probe can be, e.g., IL-13 (e.g., human IL-13), a fragment of IL-13 that specifically binds the IL-13 receptor, a mutant form of IL-13 that specifically binds the IL-13 receptor, or an antibody that specifically binds
  • the probe can be conjugated with a detectable label such as a radioactive
  • an enzyme an enzyme, a fluorescent label, or a radio-opaque label.
  • the invention features a kit for classifying a brain tumor by type or
  • the kit includes a probe that specifically binds an IL-13 receptor; and instructions for using the kit to classify a brain tumor by type or grade.
  • binding means that one molecule
  • a first molecule recognizes and adheres to a particular second molecule in a sample, but does not substantially recognize or adhere to other structurally unrelated molecules in the sample.
  • a first molecule recognizes and adheres to a particular second molecule in a sample, but does not substantially recognize or adhere to other structurally unrelated molecules in the sample.
  • antibody any antigen-binding peptide derived from an
  • immunoglobulin includes polyclonal antisera, monoclonal antibodies, fragments of immunoglobulins produced by enzymatic digestion (e.g., Fab fragments) or genetic
  • mutant means a modified version of the native
  • a native protein is one found in nature.
  • a protein may be modified by amino acid substitution, deletion, addition, permutation (e.g., circular permutation), etc. "Functional"
  • mutants retain a biological characteristic of the native protein (e.g., the capability of binding
  • the invention encompasses compositions and methods for diagnosing the type and/or
  • the grade of a brain tumor is assessed for assessing the prognosis of a patient having a brain tumor.
  • Immunological methods e.g., preparation of antigen-specific antibodies, immunoprecipitation, and immunoblotting are described, e.g., in Current Protocols in
  • Methods within the invention include a step of providing a sample of tissue isolated
  • the subject from which the sample is taken will generally be
  • a patient having a brain tumor although the subject can also be a non-human animal such as a
  • the subject may be an animal (e.g., a rodent such as an athymic or SCID mouse or rat) into which a tumor has been created such as by xenografting human brain
  • a sample of the tumor can be isolated from a subject by any conventional means.
  • a biopsy of a brain tumor in a human patient can be obtained by
  • Methods of the invention also include a step of quantifying the expression of an IL-13 receptor on a brain tumor tissue sample. Numerous methods for characterizing receptor
  • the cell or sample is contacted with the probe
  • the probe can feature a detectable label such as a radioactive, enzymatic, fluorescent, or radio-opaque (e.g., gold particle) label.
  • a detectable label such as a radioactive, enzymatic, fluorescent, or radio-opaque (e.g., gold particle) label.
  • probes that can be used to quantify IL-13 receptor expression include IL-13 itself (or fragments or mutants thereof that retain the ability to specifically bind the IL-13 receptor) and antibodies (e.g., monoclonal or polyclonal antibodies or fragments thereof) that specifically bind an IL-13 receptor.
  • IL-13 itself (or fragments or mutants thereof that retain the ability to specifically bind the IL-13 receptor) and antibodies (e.g., monoclonal or polyclonal antibodies or fragments thereof) that specifically bind an IL-13 receptor.
  • shared receptors that bind both IL-13
  • IL-4 interleukin 4
  • a particularly preferred probe is one that detects an IL-13
  • an IL-13 restrictive receptor e.g., the IL-13 receptor
  • the cells or samples being analyzed can be pre-incubated with unlabeled IL-4 as described in
  • Any suitable method for quantifying the amount of a receptor in a sample may be used in the invention.
  • receptor include: immunohistochemistry, enzyme-linked immunosorbent assay (ELISA),
  • RIA radioimmunoassay
  • direct or indirect immunofluoroscence analysis e.g., fluorescence
  • a preferred method for quantifying the amount of IL-13 receptor in the sample includes the steps of contacting a tissue section with a radiolabeled probe that specifically binds an IL-13 receptor (e.g., 125-1
  • IL-13 receptor in the sample is direct or indirect immunofluoroscence analysis using either a fluorescently labeled antibody that binds an IL-13 receptor, or fluorescently
  • the amount of IL-13 receptor in the sample are Western blotting, ELISA, and RIA.
  • the amount of IL-13 expressed by a cell or tissue sample can be approximated by measuring the amount of mRNA encoding an IL-13 receptor in the sample.
  • Numerous methods for measuring the amount of mRNA in a cell or tissue sample are known. For example, quantitative PCR analysis or Northern blotting could be used.
  • Various methods of the invention include a step of correlating the amount of IL-13
  • IL-13 binding was present in low grade gliomas, medulloblastomas or meningiomas.
  • higher expression of the IL-13 receptor on the sample appears to correlate with increased likelihood that the tumor is a higher grade brain tumor
  • the invention also provides a method of correlating the
  • the invention also provides kits for diagnosing the type and/or grade of a brain tumor.
  • the kit includes a probe that specifically binds to an IL-13 receptor, a means for detecting the probe (e.g., a detectable label that is associated with the probe or can be caused to bind the probe).
  • a means for detecting the probe e.g., a detectable label that is associated with the probe or can be caused to bind the probe.
  • the kit can also include other components
  • components might include a substrate to which the cell or tissue sample can be immobilized, e.g., a glass slide or a microtiter plate; or reagents for visualizing the detectable label.
  • E. coli BL21 ( ⁇ DE3) cells were cultured in E. coli BL21 ( ⁇ DE3) cells.
  • Brain tumor samples were obtained from patients undergoing surgical decompression at Perm State University and University of Alabama at Birmingham
  • labeled sections were apposed to Kodak autoradiography film at -70 °C for 1 to 3 days on average.
  • 5x10 4 cells were placed on a sterile glass slide in a small volume of media and allowed to attach. The cells were maintained overnight at 37
  • GBMs astrocytomas
  • astrocytomas such as oligodendrogliomas, ependymomas,
  • medulloblastoma brain tissue samples and one ganglioglioma tested showed appreciable affinity for 125 I-hIL-13.
  • the examined tissues showed variable retention of 125 I-hIL-13, which
  • gliosarcomas were positive for an IL-4-independent receptor for IL-13, but not acoustic neuroma, choroid plexus papilloma, or rhabdomyosarcoma.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Pathology (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Oncology (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • Wood Science & Technology (AREA)
  • Food Science & Technology (AREA)
  • Hospice & Palliative Care (AREA)
  • General Physics & Mathematics (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention concerne un procédé permettant de classer une tumeur au cerveau par type ou degré. Ce procédé consiste à quantifier l'expression d'un récepteur IL-13 dans un échantillon de la tumeur.
PCT/US2001/020615 2000-06-30 2001-06-28 Caracterisation d'une tumeur au cerveau WO2002002799A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001268744A AU2001268744A1 (en) 2000-06-30 2001-06-28 Characterizing a brain tumor

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US21562300P 2000-06-30 2000-06-30
US60/215,623 2000-06-30

Publications (1)

Publication Number Publication Date
WO2002002799A1 true WO2002002799A1 (fr) 2002-01-10

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002061144A2 (fr) * 2001-01-31 2002-08-08 Whitehead Institute For Biomedical Research Diagnostic de tumeur cerebrale et prediction de resultat de traitement
EP1669451A1 (fr) * 2003-09-01 2006-06-14 Japan Science and Technology Agency Marqueur de tumeur cerebrale et procede pour diagnostiquer une tumeur cerebrale
EP1999269A2 (fr) * 2006-03-08 2008-12-10 Wake Forest University Health Sciences Éphrine-a1 monomère soluble
DE202010002285U1 (de) 2010-02-12 2011-08-23 Ligmatech Automationssysteme Gmbh Vorrichtung zum Rückführen von bearbeiteten Werkstücken
US8343461B2 (en) 2006-03-08 2013-01-01 Wake Forest University Health Sciences Molecular signature of cancer

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
DEBINSKI ET AL.: "Expression of a restrictive receptor for interleukin 13 is associated with glial transformation", JOURNAL OF NEURO-ONCOLOGY, vol. 48, June 2000 (2000-06-01), pages 103 - 111, XP002946433 *
DEBINSKI ET AL.: "Molecular expression analysis of restrictive receptor for interleukin 13, a brain tumor-associated cancer/testis antigen", MOLECULAR MEDICINE, vol. 6, no. 5, 2000, pages 440 - 449, XP002946429 *
DEBINSKI ET AL.: "Receptor for interleukin 13 is a marker and therapeutic target for human high-grade gliomas", CLINICAL CANCER RESEARCH, vol. 5, May 1999 (1999-05-01), pages 985 - 990, XP002946434 *
DEBINSKI W. ET AL.: "Receptor for interleukin (IL) 13 does not interact with IL4 but receptor IL4 interacts with IL13 on human glioma cells", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 271, no. 37, 13 September 1996 (1996-09-13), pages 22426 - 22433, XP002946430 *
DEBINSKI W.: "An immune regulatory cytokine receptor and glioblastoma multiforme: An unexpected link", CRITICAL REVIEWS IN ONCOGENENSIS, vol. 9, no. 3-4, 1998, pages 255 - 268, XP002946431 *
JOSHI B.H. ET AL.: "Interleukin-13 receptor alpha chain: A novel tumor-associated transmembrane protein in primary explants of human malignant gliomas", CANCER RESEARCH, vol. 60, 1 March 2000 (2000-03-01), pages 1168 - 1172, XP002946432 *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002061144A2 (fr) * 2001-01-31 2002-08-08 Whitehead Institute For Biomedical Research Diagnostic de tumeur cerebrale et prediction de resultat de traitement
WO2002061144A3 (fr) * 2001-01-31 2003-03-27 Whitehead Biomedical Inst Diagnostic de tumeur cerebrale et prediction de resultat de traitement
EP1669451A1 (fr) * 2003-09-01 2006-06-14 Japan Science and Technology Agency Marqueur de tumeur cerebrale et procede pour diagnostiquer une tumeur cerebrale
EP1669451A4 (fr) * 2003-09-01 2007-02-14 Japan Science & Tech Agency Marqueur de tumeur cerebrale et procede pour diagnostiquer une tumeur cerebrale
EP2946786A1 (fr) * 2006-03-08 2015-11-25 Wake Forest University Health Sciences Récepteur Ephrin A1 monomère soluble
EP1999269A4 (fr) * 2006-03-08 2009-06-17 Univ Wake Forest Health Sciences Éphrine-a1 monomère soluble
US8343461B2 (en) 2006-03-08 2013-01-01 Wake Forest University Health Sciences Molecular signature of cancer
EP1999269A2 (fr) * 2006-03-08 2008-12-10 Wake Forest University Health Sciences Éphrine-a1 monomère soluble
US9290558B2 (en) 2006-03-08 2016-03-22 Wake Forest University Health Sciences Molecular signature of cancer
US9974830B2 (en) 2006-03-08 2018-05-22 Wake Forest University Health Sciences Molecular signature of cancer
US11207380B2 (en) 2006-03-08 2021-12-28 Wake Forest University Health Sciences Molecular signature of cancer
DE202010002285U1 (de) 2010-02-12 2011-08-23 Ligmatech Automationssysteme Gmbh Vorrichtung zum Rückführen von bearbeiteten Werkstücken
EP2360108A1 (fr) 2010-02-12 2011-08-24 Ligmatech Automationssysteme GmbH Dispositif de récupération de pièces usinées traitées

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Publication number Publication date
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