WO1999003992A1 - Recepteur de proteine trail - Google Patents

Recepteur de proteine trail Download PDF

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Publication number
WO1999003992A1
WO1999003992A1 PCT/US1998/014410 US9814410W WO9903992A1 WO 1999003992 A1 WO1999003992 A1 WO 1999003992A1 US 9814410 W US9814410 W US 9814410W WO 9903992 A1 WO9903992 A1 WO 9903992A1
Authority
WO
WIPO (PCT)
Prior art keywords
trail
polypeptide
trall
residues
dna
Prior art date
Application number
PCT/US1998/014410
Other languages
English (en)
Inventor
Mariapia Degli-Esposti
Original Assignee
Immunex 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 Immunex Corporation filed Critical Immunex Corporation
Priority to EP98934441A priority Critical patent/EP0998561A4/fr
Priority to CA002295719A priority patent/CA2295719A1/fr
Priority to NZ501951A priority patent/NZ501951A/en
Priority to IL13392098A priority patent/IL133920A0/xx
Priority to AU83957/98A priority patent/AU8395798A/en
Priority to JP2000503198A priority patent/JP2001510042A/ja
Publication of WO1999003992A1 publication Critical patent/WO1999003992A1/fr

Links

Classifications

    • 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
    • C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence

Definitions

  • TRAIL TRAIL
  • Certain uses of TRAIL-R flow from this ability to bind TRALL, as discussed further below.
  • TRAIL-R finds use in inhibiting biological activities of TRAIL, or in purifying TRAIL by affinity chromatography, for example.
  • TRAIL-R protein or immunogenic fragments thereof may be employed as immunogens to generate antibodies that are immunoreactive therewith.
  • the antibodies are monoclonal antibodies.
  • the present invention encompasses TRAIL-R in various forms, including those that are naturally occurring or produced through various techniques such as procedures involving recombinant DNA technology.
  • forms of TRAIL-R include, but are not limited to, fragments, derivatives, variants, and oligomers of TRAIL-R, as well as fusion proteins containing TRAIL-R or fragments thereof.
  • a protein preparation may include a mixture of protein molecules having different N-terminal amino acids, resulting from cleavage of the signal peptide at more than one site.
  • the TRAIL-R-encoding DNAs of the present invention include variants that differ from a native TRAIL-R DNA sequence because of one or more deletions, insertions or substitutions, but that encode a biologically active TRAIL-R polypeptide.
  • One biological activity of TRAIL-R is the ability to bind TRAIL.
  • a variant TRAIL-R polypeptide differs in amino acid sequence from a native TRAIL-R, but is substantially equivalent to a native TRAIL-R in a biological activity.
  • a variant TRAIL-R that binds TRAIL with essentially the same binding affinity as does a native TRAIL-R. Binding affinity can be measured by conventional procedures, e.g., as described in U.S. Patent no. 5,512,457.
  • a promoter nucleotide sequence is operably linked to an TRAIL-R DNA sequence if the promoter nucleotide sequence controls the transcription of the TRAIL-R DNA sequence.
  • An origin of replication that confers the ability to replicate in the desired host cells, and a selection gene by which transformants are identified, are generally incorporated into the expression vector.
  • glycolytic enzymes Hess et al., J. Adv. Enzyme Reg. 7: 149, 1968; and Holland et al., Biochem. 17:4900, 1978
  • enolase glyceraldehyde-3-phosphate dehydrogenase
  • hexokinase hexokinase
  • pyruvate decarboxylase phosphofructokinase
  • glucose-6-phosphate isomerase 3 -phosphogly cerate mutase
  • pyruvate kinase triosephosphate isomerase
  • phospho-glucose isomerase phospho-glucose isomerase
  • glucokinase glucokinase
  • the culture medium first may be concentrated using a commercially available protein concentration filter, for example, an Amicon or Millipore Pellicon ultrafiltration unit.
  • a purification matrix such as a gel filtration matrix.
  • an anion exchange resin can be employed, for example, a matrix or substrate having pendant diethylaminoethyl (DEAE) groups.
  • the matrices can be acrylamide, agarose, dextran, cellulose or other support materials commonly employed in protein purification.
  • a cation exchange step can be employed.
  • Recombinant protein produced in bacterial culture can be isolated by initial disruption of the host cells, centrifugation, extraction from cell pellets if an insoluble polypeptide, or from the supernatant fluid if a soluble polypeptide, followed by one or more concentration, salting-out, ion exchange, affinity purification or size exclusion chromatography steps. Finally, RP-HPLC can be employed for final purification steps. Microbial cells can be disrupted by any convenient method, including freeze-thaw cycling, sonication, mechanical disruption, or use of cell lysing agents.
  • TRAIL-R oligomers that contain TRAIL-R polypeptides.
  • TRAIL-R oligomers may be in the form of covalently-linked or non- covalently-linked dimers, trimers, or higher oligomers.
  • the oligomers comprise from two to four TRAIL-R polypeptides.
  • the TRAIL-R moieties of the oligomer may be soluble polypeptides, as described above.
  • TRAIL-R finds use as a protein purification reagent.
  • TRAIL-R polypeptides may be attached to a solid support material and used to purify TRAIL proteins by affinity chromatography.
  • a TRAIL-R polypeptide (in any form described herein that is capable of binding TRALL) is attached to a solid support by conventional procedures.
  • chromatography columns containing functional groups that will react with functional groups on amino acid side chains of proteins are available (Pharmacia Biotech, Inc., Piscataway, NJ).
  • a TRAIL-R/Fc protein is attached to Protein A- or Protein G-containing chromatography columns through interaction with the Fc moiety.
  • Another embodiment of the present invention is directed to the use of TRAIL-R to reduce TRAIL-mediated death of T cells in HIV-infected patients.
  • the role of T cell apoptosis in the development of AIDS has been the subject of a number of studies (see, for example, Meyaard et al., Science 257:217-219, 1992; Groux et al., J Exp. Med., 175:331, 1992; and Oyaizu et al., in Cell Activation and Apoptosis in HIV Infection, Andrieu and Lu, Eds., Plenum Press, New York, 1995, pp. 101-114).
  • TRAIL-R can be combined in admixture, either as the sole active material or with other known active materials suitable for a given indication, with pharmaceutically acceptable diluents (e.g., saline, Tris-HCl, acetate, and phosphate buffered solutions), preservatives (e.g., thimerosal, benzyl alcohol, parabens), emulsifiers, solubilizers, adjuvants and/or carriers.
  • Suitable formulations for pharmaceutical compositions include those described in Remington's Pharmaceutical Sciences, 16th ed. 1980, Mack Publishing Company, East on, PA.
  • compositions of the present invention may contain a TRAIL-R polypeptide in any form described herein, such as native proteins, variants, derivatives, oligomers, and biologically active fragments.
  • the composition comprises a soluble TRAIL-R polypeptide or an oligomer comprising soluble TRAIL-R polypeptides.
  • TRAIL-R nucleotide sequences comprise at least about 30, or at least 60, contiguous nucleotides of a TRALL-R DNA sequence.
  • Nucleic acids provided herein include DNA and RNA complements of said fragments, along with both single-stranded and double- stranded forms of the TRALL-R DNA.
  • Other useful fragments of the TRALL-R nucleic acids include antisense or sense oligonucleotides comprising a single-stranded nucleic acid sequence (either RNA or DNA) capable of binding to target TRALL-R mRNA (sense) or TRALL-R DNA (antisense) sequences.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Toxicology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Cell Biology (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Cette invention se rapporte à une protéine appelée récepteur de TRAIL (TRAIL-R) qui se lie à la protéine connue comme ligand induisant l'apoptose et associée au TNF (TRAIL TNF-related apoptosis-inducing ligand). Ce récepteur de TRAIL s'avère utile pour purifier la protéine TRAIL ou pour inhiber les activités de cette protéine. Cette invention se rapporte aussi à des séquences d'ADN isolées qui codent les polypeptides de TRAIL-R, ainsi qu'à des vecteurs d'expression contenant ces séquences d'ADN, et à des cellules hôtes transformées par de tels vecteurs d'expression recombinés. Cette invention se rapporte enfin à des anticorps qui sont immunoréactifs vis à vis du récepteur TRAIL-R.
PCT/US1998/014410 1997-07-15 1998-07-10 Recepteur de proteine trail WO1999003992A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP98934441A EP0998561A4 (fr) 1997-07-15 1998-07-10 Recepteur de proteine trail
CA002295719A CA2295719A1 (fr) 1997-07-15 1998-07-10 Recepteur de proteine trail
NZ501951A NZ501951A (en) 1997-07-15 1998-07-10 TRAIL-R receptor polypeptide, DNA encoding a nucleotide sequence of the peptide, compositions and antibodies thereof
IL13392098A IL133920A0 (en) 1997-07-15 1998-07-10 Trail receptor
AU83957/98A AU8395798A (en) 1997-07-15 1998-07-10 Trail receptor
JP2000503198A JP2001510042A (ja) 1997-07-15 1998-07-10 Ｔｒａｉｌ受容体

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US89211997A 1997-07-15 1997-07-15
US08/892,119 1997-07-15

Publications (1)

Publication Number Publication Date
WO1999003992A1 true WO1999003992A1 (fr) 1999-01-28

Family

ID=25399402

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/014410 WO1999003992A1 (fr) 1997-07-15 1998-07-10 Recepteur de proteine trail

Country Status (7)

Country Link
EP (1) EP0998561A4 (fr)
JP (1) JP2001510042A (fr)
AU (1) AU8395798A (fr)
CA (1) CA2295719A1 (fr)
IL (1) IL133920A0 (fr)
NZ (1) NZ501951A (fr)
WO (1) WO1999003992A1 (fr)

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6214580B1 (en) 1997-05-30 2001-04-10 Human Genome Sciences, Inc. Human tumor necrosis factor receptor tr10
US6252050B1 (en) * 1998-06-12 2001-06-26 Genentech, Inc. Method for making monoclonal antibodies and cross-reactive antibodies obtainable by the method
WO2001083560A1 (fr) * 2000-05-02 2001-11-08 Uab Research Foundation Un anticorps selectif pour un recepteur de ligand induisant l'apoptose en relation avec le facteur de necrose tumorale et ses utilisations
EP1187842A1 (fr) * 1999-05-28 2002-03-20 Human Genome Sciences, Inc. Tr10, recepteur de facteur de necrose tumorale humain
WO2002053727A1 (fr) * 2000-12-29 2002-07-11 Dong Wha Pharm. Ind. Co., Ltd. Cristallographie rayons x de la structure tridimensionnelles du facteur d'apoptose humains et de son récepteur et protéine de suppression du ligand trail mutante
WO2002097033A2 (fr) 2001-05-25 2002-12-05 Human Genome Sciences, Inc. Anticorps se liant de maniere immunospecifique a des recepteurs de trail
US6506569B1 (en) 1997-05-30 2003-01-14 Human Genome Sciences, Inc. Antibodies to human tumor necrosis factor receptor TR10
KR100436089B1 (ko) * 2000-07-06 2004-06-14 설대우 분비성 재조합 트라이머형의 트레일 단백질 생산을 위한 디엔에이 카세트, 테트라사이클린/독시사이클린-유도성아데노-관련 바이러스 벡터, 이 둘의 조합, 및 이들을이용한 유전자 치료
US7118863B2 (en) 1999-08-04 2006-10-10 Amgen, Inc. Methods for detecting NTR3 nucleic acids by hybridization
US7279160B2 (en) 2000-05-02 2007-10-09 The Uab Research Foundation Combinations of DR5 antibodies and other therapeutic agents
US7320796B2 (en) 1999-07-09 2008-01-22 Amgen Inc. Isolation, identification and characterization of tmst2, a novel member of the TNF-receptor supergene family
US7476383B2 (en) 2000-05-02 2009-01-13 The Uab Research Foundation Antibody selective for DR4 and uses thereof
US7544519B2 (en) 1999-08-04 2009-06-09 Amgen Inc. Fhm a novel member of the TNF ligand supergene family: materials and methods for interaction modulators
WO2011057099A2 (fr) 2009-11-05 2011-05-12 The Uab Research Foundation Traitement de cancers à génotype de type basal
US8129124B2 (en) 2005-02-02 2012-03-06 The Uab Research Foundation Agents and methods related to reducing resistance to apoptosis-inducing death receptor agonists
US8703712B2 (en) 2010-03-18 2014-04-22 The Uab Research Foundation Targeting cancer stem cells with DR5 agonists

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6214580B1 (en) * 1997-05-30 2001-04-10 Human Genome Sciences, Inc. Human tumor necrosis factor receptor tr10
JP2001513994A (ja) * 1997-08-26 2001-09-11 ジェネンテク・インコーポレイテッド Ｒｔｄレセプター

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
GOLSTEIN P.: "CELL DEATH: TRAIL AND ITS RECEPTORS.", CURRENT BIOLOGY, CURRENT SCIENCE, GB, vol. 07., no. 12., 1 December 1997 (1997-12-01), GB, pages R750 - R753., XP002912781, ISSN: 0960-9822, DOI: 10.1016/S0960-9822(06)00395-2 *
MARSTERS S. A., ET AL.: "A NOVEL RECEPTOR FOR APO2L/TRAIL CONTAINS A TRUNCATED DEATH DOMAIN.", CURRENT BIOLOGY, CURRENT SCIENCE, GB, vol. 07., no. 12., 1 December 1997 (1997-12-01), GB, pages 1003 - 1006., XP002912780, ISSN: 0960-9822, DOI: 10.1016/S0960-9822(06)00422-2 *
PAN G., ET AL.: "THE RECEPTOR FOR THE CYTOTOXIC LIGAND TRAIL.", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, US, vol. 276., 4 April 1997 (1997-04-04), US, pages 111 - 113., XP002912779, ISSN: 0036-8075, DOI: 10.1126/science.276.5309.111 *
See also references of EP0998561A4 *

Cited By (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6214580B1 (en) 1997-05-30 2001-04-10 Human Genome Sciences, Inc. Human tumor necrosis factor receptor tr10
US7465707B2 (en) 1997-05-30 2008-12-16 Human Genome Sciences, Inc. Methods of treatment with TR10 polypeptides
US6969599B2 (en) 1997-05-30 2005-11-29 Human Genome Sciences, Inc. Nucleic acids encoding tumor necrosis factor receptor TR10
US6506569B1 (en) 1997-05-30 2003-01-14 Human Genome Sciences, Inc. Antibodies to human tumor necrosis factor receptor TR10
US6607726B1 (en) 1997-05-30 2003-08-19 Human Genome Sciences, Inc. Human tumor necrosis factor receptor TR10
US6252050B1 (en) * 1998-06-12 2001-06-26 Genentech, Inc. Method for making monoclonal antibodies and cross-reactive antibodies obtainable by the method
US7592439B2 (en) 1998-06-12 2009-09-22 Genentech, Inc. Method for making monoclonal antibodies and cross-reactive antibodies obtainable by the method
EP1187842A1 (fr) * 1999-05-28 2002-03-20 Human Genome Sciences, Inc. Tr10, recepteur de facteur de necrose tumorale humain
EP1187842A4 (fr) * 1999-05-28 2004-03-03 Human Genome Sciences Inc Tr10, recepteur de facteur de necrose tumorale humain
US7320796B2 (en) 1999-07-09 2008-01-22 Amgen Inc. Isolation, identification and characterization of tmst2, a novel member of the TNF-receptor supergene family
US7544519B2 (en) 1999-08-04 2009-06-09 Amgen Inc. Fhm a novel member of the TNF ligand supergene family: materials and methods for interaction modulators
US7118863B2 (en) 1999-08-04 2006-10-10 Amgen, Inc. Methods for detecting NTR3 nucleic acids by hybridization
EP2065401A3 (fr) * 2000-05-02 2009-07-22 UAB Research Foundation Sélecteur d'anticorps pour un récepteur de ligand induisant l'apoptose associée au facteur de nécrose de tumeur et utilisations associées
US7704502B2 (en) 2000-05-02 2010-04-27 The Uab Research Foundation Combinations of antibodies selective for DR5 and other therapeutic agents
US8715668B2 (en) 2000-05-02 2014-05-06 The Uab Research Foundation Antibody selective for a tumor necrosis factor-related apoptosis-inducing ligand receptor DR5 and uses thereof
CZ306996B6 (cs) * 2000-05-02 2017-11-01 Uab Research Foundation Čištěná protilátka, která specificky váže TRAIL receptor pro DR5
US7476383B2 (en) 2000-05-02 2009-01-13 The Uab Research Foundation Antibody selective for DR4 and uses thereof
US7244429B2 (en) 2000-05-02 2007-07-17 The Uab Research Foundation Antibody selective for a tumor necrosis factor-related apoptosis-inducing ligand receptor and uses thereof
US9700618B2 (en) 2000-05-02 2017-07-11 The Uab Research Foundation Antibody selective for a tumor necrosis factor-related apoptosis-inducing ligand receptor and uses thereof
WO2001083560A1 (fr) * 2000-05-02 2001-11-08 Uab Research Foundation Un anticorps selectif pour un recepteur de ligand induisant l'apoptose en relation avec le facteur de necrose tumorale et ses utilisations
CN101585881A (zh) * 2000-05-02 2009-11-25 Uab研究基金会 对于肿瘤坏死因子相关细胞凋亡诱导配体受体选择性的抗体及其应用
US7279160B2 (en) 2000-05-02 2007-10-09 The Uab Research Foundation Combinations of DR5 antibodies and other therapeutic agents
US7790165B2 (en) 2000-05-02 2010-09-07 The Uab Research Foundation Antibody selective for a tumor necrosis factor-related apoptosis-inducing ligand receptor and uses thereof
CN101585881B (zh) * 2000-05-02 2014-11-26 Uab研究基金会 对于肿瘤坏死因子相关细胞凋亡诱导配体受体选择性的抗体及其应用
US7981421B2 (en) 2000-05-02 2011-07-19 The Uab Research Foundation Combinations of antibodies selective for DR5 and other therapeutic agents
EP2368910A1 (fr) * 2000-05-02 2011-09-28 UAB Research Foundation Sélecteur d'anticorps pour un récepteur de ligand induisant l'apoptose associée au facteur de nécrose de tumeur et utilisations associées
US8067001B2 (en) 2000-05-02 2011-11-29 The Uab Research Foundation Antibody selective for a tumor necrosis factor-related apoptosis-inducing ligand receptor and uses thereof
CZ304614B6 (cs) * 2000-05-02 2014-08-06 Uab Research Foundation Čištěná protilátka a polypeptid, prostředek selektivně indukující buněčnou smrt, neukleová kyselina, vektor s jejím obsahem, kultivovaná buňka, kit pro indukci apoptosy, transformovaná E. coli, způsob produkce a použití
US8329180B2 (en) 2000-05-02 2012-12-11 The Uab Research Foundation Antibody selective for a tumor necrosis factor-related apoptosis-inducing ligand receptor and uses thereof
KR100436089B1 (ko) * 2000-07-06 2004-06-14 설대우 분비성 재조합 트라이머형의 트레일 단백질 생산을 위한 디엔에이 카세트, 테트라사이클린/독시사이클린-유도성아데노-관련 바이러스 벡터, 이 둘의 조합, 및 이들을이용한 유전자 치료
WO2002053727A1 (fr) * 2000-12-29 2002-07-11 Dong Wha Pharm. Ind. Co., Ltd. Cristallographie rayons x de la structure tridimensionnelles du facteur d'apoptose humains et de son récepteur et protéine de suppression du ligand trail mutante
WO2002097033A2 (fr) 2001-05-25 2002-12-05 Human Genome Sciences, Inc. Anticorps se liant de maniere immunospecifique a des recepteurs de trail
US8476030B2 (en) 2005-02-02 2013-07-02 The Uab Research Foundation Agents and methods related to reducing resistance to apoptosis-inducing death receptor agonists
US8129124B2 (en) 2005-02-02 2012-03-06 The Uab Research Foundation Agents and methods related to reducing resistance to apoptosis-inducing death receptor agonists
US9528993B2 (en) 2005-02-02 2016-12-27 The Uab Research Foundation Agents and methods related to screening for resistance to DR5 and reducing resistance to DR5 agonists
WO2011057099A2 (fr) 2009-11-05 2011-05-12 The Uab Research Foundation Traitement de cancers à génotype de type basal
US9527915B2 (en) 2009-11-05 2016-12-27 The Uab Research Foundation Treating basal-like genotype cancers
US10316100B2 (en) 2009-11-05 2019-06-11 The Uab Research Foundation Treating basal-like genotype cancers
US8703712B2 (en) 2010-03-18 2014-04-22 The Uab Research Foundation Targeting cancer stem cells with DR5 agonists

Also Published As

Publication number Publication date
CA2295719A1 (fr) 1999-01-28
EP0998561A1 (fr) 2000-05-10
IL133920A0 (en) 2001-04-30
AU8395798A (en) 1999-02-10
NZ501951A (en) 2001-09-28
JP2001510042A (ja) 2001-07-31
EP0998561A4 (fr) 2004-08-18

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