CA2365533A1 - Diagnosis and treatment of neuroectodermal tumors - Google Patents

Diagnosis and treatment of neuroectodermal tumors Download PDF

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Publication number
CA2365533A1
CA2365533A1 CA002365533A CA2365533A CA2365533A1 CA 2365533 A1 CA2365533 A1 CA 2365533A1 CA 002365533 A CA002365533 A CA 002365533A CA 2365533 A CA2365533 A CA 2365533A CA 2365533 A1 CA2365533 A1 CA 2365533A1
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Canada
Prior art keywords
chlorotoxin
tissue
group
labeled
neoplastic
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.)
Granted
Application number
CA002365533A
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French (fr)
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CA2365533C (en
Inventor
Harald W. Sontheimer
Susan A. Lyons
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UAB Research Foundation
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The Uab Research Foundation
Harald W. Sontheimer
Susan A. Lyons
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Application filed by The Uab Research Foundation, Harald W. Sontheimer, Susan A. Lyons filed Critical The Uab Research Foundation
Publication of CA2365533A1 publication Critical patent/CA2365533A1/en
Application granted granted Critical
Publication of CA2365533C publication Critical patent/CA2365533C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • G01N33/57492—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds localized on the membrane of tumor or cancer cells
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/811—Test for named disease, body condition or organ function
    • Y10S436/813—Cancer

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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)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Cell Biology (AREA)
  • Oncology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Organic Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Hospice & Palliative Care (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • Microbiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Toxicology (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention provides fusion proteins for the detection and treatme nt of neuroectodermal tumors. Previous work demonstrated that chlorotoxin is specific for glial-derived or meningioma-derived tumor cells. The current invention has extended the use of chlorotoxin-cytotoxin fusion proteins to treat the whole class neuroectodermal tumors such as gliomas, meningiomas, ependymonas, medulloblastomas, neuroblastomas, gangliomas, pheochromocytomas , melanomas, PPNET's, small cell carcinoma of the lung, Ewing's sarcoma, and metastatic tumors in the brain. Also, diagnostic methods are provided for screening neoplastic neuroectodermal tumors.

Claims (14)

1. A method of treating an individual having a neuroectodermal tumor, comprising the step of:
administering a pharmaceutical composition comprising a pharmaceutically effective dose of a neuroectodermal tumor specific ligand fused to a cytotoxic moiety and a pharmaceutically acceptable carrier.
2. The method of claim 1, wherein the neuroectodermal tumor is a tumor type treated is selected from the group consisting of ependymonas, medulloblastomas, neuroblastomas, gangliomas, pheochromocytomas, melanomas, peripheral primitive neuroectodermal tumors, small cell carcinoma of the lung, Ewing's sarcoma, and metastatic tumors in the brain.
3. The method of claim 1, wherein the neuroectodermal tumor specific ligand is chlorotoxin.
4. The method of claim 3, wherein said chlorotoxin is selected from the group consisting of native chlorotoxin, synthetic chlorotoxin and recombinant chlorotoxin.
5. The method of claim 1, wherein said cytotoxic moieties is selected from the group consisting of gelonin, ricin, saponin, pseudonomas exotoxin, pokeweed antiviral protein, diphtheria toxin, and complement proteins.
6. The method of claim 1, wherein the neuroectodermal tumor specific ligand is an antibody against the chlorotoxin receptor.
7. A method of differentiating neuroectodermal tumor-derived neoplastic tumor tissue from non-neoplastic tissue, comprising the steps of:
contacting a tissue of interest with labeled chlorotoxin which binds specifically to neuroectodermal tumor neoplastic tumor tissue; and measuring the binding of the labeled chlorotoxin, wherein an elevated level of binding, relative to normal tissue, indicates that the tissue is neoplastic.
8. The method of claim 7, wherein said chlorotoxin is labeled with a detection moiety.
9. The method of claim 8, wherein said detection moiety is selected from the group consisting of a fluroschrome, biotin, a colorimetric agent linked to an enzyme substrate.
10. The method of claim 8, wherein said labeled chlorotoxin binding is determined by a method selected from the group consisting of fluorescent microscopy, ELIZA and fluorescent activated cell sorting.
11. The method of claim 7, wherein said labeled chlorotoxin is radiolabeled.
12. The method of claim 11, wherein said radiolabeled chlorotoxin is selected from the group consisting of 131I-chlorotoxin and 125I-chlorotoxin.
13. The method of claim 7, wherein the level of radiolabeled chlorotoxin binding affinity indicative of neoplastic tissue is from about 5 nanomolar to about 5 micromolar.
14. The method of claim 13, wherein said labeled chlorotoxin binding is determined using positron emission tomography scanning.
CA2365533A 1999-04-21 2000-04-19 Diagnosis and treatment of neuroectodermal tumors Expired - Lifetime CA2365533C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US09/296,031 1999-04-21
US09/296,031 US6667156B2 (en) 1995-12-27 1999-04-21 Diagnosis and treatment of neuroectodermal tumors
PCT/US2000/010453 WO2000062807A1 (en) 1999-04-21 2000-04-19 Diagnosis and treatment of neuroectodermal tumors

Publications (2)

Publication Number Publication Date
CA2365533A1 true CA2365533A1 (en) 2000-10-26
CA2365533C CA2365533C (en) 2012-11-06

Family

ID=23140309

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2365533A Expired - Lifetime CA2365533C (en) 1999-04-21 2000-04-19 Diagnosis and treatment of neuroectodermal tumors

Country Status (10)

Country Link
US (4) US6667156B2 (en)
EP (1) EP1200123B1 (en)
JP (1) JP2002542206A (en)
CN (1) CN1377280A (en)
AT (1) ATE308340T1 (en)
AU (1) AU777209B2 (en)
CA (1) CA2365533C (en)
DE (1) DE60023706T2 (en)
ES (1) ES2253223T3 (en)
WO (1) WO2000062807A1 (en)

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6667156B2 (en) * 1995-12-27 2003-12-23 Uab Research Foundation Diagnosis and treatment of neuroectodermal tumors
CA2494451A1 (en) * 2002-05-31 2003-12-11 Transmolecular, Inc. Treatment of cell proliferative disorders with chlorotoxin
US20060088899A1 (en) * 2002-05-31 2006-04-27 Alvarez Vernon L Combination chemotherapy with chlorotoxin
DE602006020710D1 (en) 2005-04-22 2011-04-28 Fred Hutchinson Cancer Res Foundation FLUORESCENT CHLOROTOXIN CONJUGATE AND METHOD FOR THE INTRAOPERATIVE VIEW OF CANCER
EP1934261B1 (en) * 2005-09-26 2014-10-29 Medarex, L.L.C. Human monoclonal antibodies to cd70
WO2007117467A2 (en) * 2006-03-31 2007-10-18 Transmolecular, Inc. Use of tm-601 for the diagnosis and treatment of tumors
WO2008074004A2 (en) * 2006-12-14 2008-06-19 Medarex, Inc. Human antibodies that bind cd70 and uses thereof
AU2008285364A1 (en) * 2007-08-07 2009-02-12 Transmolecular, Inc. Chlorotoxins as drug carriers
WO2009049184A2 (en) * 2007-10-12 2009-04-16 Transmolecular, Inc. Systemic administration of chlorotoxin agents for the diagnosis and treatment of tumors
US8097284B2 (en) * 2007-11-13 2012-01-17 Arthur Mikaelian Polarized scorpion venom solution and a method for making polarized scorpion venom solution
CN102438646A (en) * 2008-05-15 2012-05-02 特兰斯莫莱库拉公司 Treatment of metastatic tumors
EP2300045A1 (en) * 2008-05-15 2011-03-30 Transmolecular, Inc. Treatment of metastatic tumors
KR101923235B1 (en) 2010-02-04 2018-11-28 에이자이 아이엔씨. Chlorotoxin polypeptides and conjugates and uses thereof
CA2799169C (en) 2010-05-11 2019-07-23 Fred Hutchinson Cancer Research Center Chlorotoxin variants, conjugates, and methods for their use
US8524239B2 (en) 2010-07-09 2013-09-03 The United States of America as represented by the Secrectary, Department of Health and Human Services Photosensitizing antibody-fluorophore conjugates
CN102552943A (en) * 2010-12-31 2012-07-11 复旦大学 Tumor targeting magnetic resonance contrast medium modified by chlorotoxin and preparation method and application thereof
WO2013003507A1 (en) 2011-06-27 2013-01-03 Morphotek, Inc. Multifunctional agents
WO2014093406A1 (en) 2012-12-10 2014-06-19 Fred Hutchinson Cancer Research Center Methods for screening
US9784730B2 (en) 2013-03-21 2017-10-10 University Of Washington Through Its Center For Commercialization Nanoparticle for targeting brain tumors and delivery of O6-benzylguanine
US11559580B1 (en) 2013-09-17 2023-01-24 Blaze Bioscience, Inc. Tissue-homing peptide conjugates and methods of use thereof
JP6741599B2 (en) 2014-06-02 2020-08-19 リ−コール，インコーポレイティド Phthalocyanine probe and its use
JP6796058B2 (en) 2014-08-08 2020-12-02 ザ ユナイテッド ステイツ オブ アメリカ， アズ リプレゼンテッド バイ ザ セクレタリー， デパートメント オブ ヘルス アンド ヒューマン サービシーズ Light-controlled removal of targets in vitro and in vivo
CN104877016A (en) * 2015-04-30 2015-09-02 温州生物材料与工程研究所 Folded chlorotoxin, chlorotoxin mutant, folded chlorotoxin mutant and preparation process thereof
US9518099B1 (en) * 2015-09-13 2016-12-13 Wenzhou Institute Of Biomaterials And Engineering Refolded chlorotoxin, chlorotoxin variant, refolded chlorotoxin variant, and preparation technology thereof
JP7409741B2 (en) 2017-09-15 2024-01-09 エーザイ インク． Chlorotoxin drugs and their uses
US11866466B2 (en) 2017-12-19 2024-01-09 Blaze Bioscience, Inc. Tumor homing and cell penetrating peptide-immuno-oncology agent complexes and methods of use thereof

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EP0282581A4 (en) * 1986-09-19 1988-11-02 Scripps Clinic Res Monoclonal paratopic molecule directed to human ganglioside gd2.
CA2066428C (en) 1989-09-08 2000-11-28 Bert Vogelstein Structural alterations of the egf receptor gene in human gliomas
US5223253A (en) 1989-09-28 1993-06-29 American Home Products Corporation Bovine vaccine compositions and method for preventing trichomonas infections using same
US5750376A (en) 1991-07-08 1998-05-12 Neurospheres Holdings Ltd. In vitro growth and proliferation of genetically modified multipotent neural stem cells and their progeny
US5626862A (en) 1994-08-02 1997-05-06 Massachusetts Institute Of Technology Controlled local delivery of chemotherapeutic agents for treating solid tumors
US5756340A (en) 1995-05-08 1998-05-26 The Regents Of The University Of California Insect control with multiple toxins
US6667156B2 (en) * 1995-12-27 2003-12-23 Uab Research Foundation Diagnosis and treatment of neuroectodermal tumors
US5905027A (en) * 1995-12-27 1999-05-18 Uab Research Foundation Method of diagnosing and treating gliomas
EP2300045A1 (en) * 2008-05-15 2011-03-30 Transmolecular, Inc. Treatment of metastatic tumors

Also Published As

Publication number Publication date
WO2000062807A1 (en) 2000-10-26
JP2002542206A (en) 2002-12-10
EP1200123A4 (en) 2003-05-02
EP1200123A1 (en) 2002-05-02
EP1200123B1 (en) 2005-11-02
US6667156B2 (en) 2003-12-23
US20100215576A1 (en) 2010-08-26
US7678759B2 (en) 2010-03-16
CA2365533C (en) 2012-11-06
AU4468700A (en) 2000-11-02
ES2253223T3 (en) 2006-06-01
DE60023706T2 (en) 2006-08-03
US20020146749A1 (en) 2002-10-10
ATE308340T1 (en) 2005-11-15
DE60023706D1 (en) 2005-12-08
AU777209B2 (en) 2004-10-07
US20120183544A1 (en) 2012-07-19
CN1377280A (en) 2002-10-30
US20040141981A1 (en) 2004-07-22

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Effective date: 20200419