WO2006043362A1 - 悪性黒色腫（メラノーマ）の新規な診断キット - Google Patents

悪性黒色腫（メラノーマ）の新規な診断キット Download PDF

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Publication number
WO2006043362A1
WO2006043362A1 PCT/JP2005/014567 JP2005014567W WO2006043362A1 WO 2006043362 A1 WO2006043362 A1 WO 2006043362A1 JP 2005014567 W JP2005014567 W JP 2005014567W WO 2006043362 A1 WO2006043362 A1 WO 2006043362A1
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WIPO (PCT)
Prior art keywords
sparc
melanoma
gpc3
protein
antibody
Prior art date
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PCT/JP2005/014567
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English (en)
French (fr)
Japanese (ja)
Inventor
Yasuharu Nishimura
Tetsuya Nakatsura
Yoshiaki Ikuta
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Kumamoto University
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Application filed by Kumamoto University filed Critical Kumamoto University
Priority to US11/577,435 priority Critical patent/US8017345B2/en
Priority to DE602005016831T priority patent/DE602005016831D1/de
Priority to EP05770440A priority patent/EP1813943B1/en
Priority to AU2005297303A priority patent/AU2005297303B2/en
Priority to JP2006542257A priority patent/JP4834839B2/ja
Publication of WO2006043362A1 publication Critical patent/WO2006043362A1/ja

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Classifications

    • 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
    • G01N33/5743—Specifically defined cancers of skin, e.g. melanoma
    • 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
    • G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
    • G01N2333/4701—Details
    • G01N2333/4722—Proteoglycans, e.g. aggreccan
    • 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
    • G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
    • G01N2333/4701—Details
    • G01N2333/4727—Calcium binding proteins, e.g. calmodulin

Definitions

  • the present invention relates to a novel diagnostic kit and diagnostic method for malignant melanoma.
  • Melanoma is a type of skin cancer called malignant melanoma. Although there are various types of skin cancer, melanoma is the highest grade of skin cancer and is very feared. Among the cells that make up the skin, there are cells that produce melanin pigments, which are called pigment cells (melanocytes), but those cells that have become cancerous are melanomas.
  • melanocytes pigment cells
  • Melanoma occurs in people of all ages, but it occurs more often when people are over 40 years old, with the highest number in the 60s to 70s. Although the incidence of children is very small, it does not mean that they do not occur, and there is a tendency that young people in the 20s to 30s have been increasing recently. Genders tend to be more common in both men and women. The area where Japanese melanoma is likely to occur accounts for about 30%, where the sole of the foot (the back of the foot) is the most common. A feature of the Japanese is that they can do a lot on the toes and fingernails. In addition, it occurs on any skin, including the body, hands, feet, face, and head, as in Westerners.
  • glypican-3 (Glypican-3; GPC3) secretory protein, which was detected in the serum of 40% hepatocellular carcinoma patients and 40% melanoma patients using ELISA.
  • GPC3 glypican-3; GPC3
  • can be detected and reported to be useful as a new tumor marker for hepatocellular carcinoma Nakatsura, T. et al., Biochem. Biophys. Res. Commun. 306, 16-25, 2003; and Nakatsura, T. et al., Clin. Cancer Res. 10,6612-6621, 2004).
  • SPARC Secreted protein, acidic rich in cysteine
  • BM-40 additional name osteonectin
  • SPARC is a cell interstitial glycoprotein having various functions. Its main functions include cell adhesion prevention, cell growth inhibition, and cell stroma regulation. (Bradshaw and Sage, J. Clin. Invest, 107: 1049-1054,2001; and Brekken and Sage, Matrix Biol., 2001; 19: 816 -827) Cells by binding interstitial structural proteins such as collagen It regulates the interaction between the stroma and the cells.
  • SPARC in adults is highly expressed in sites where bones, platelets, wound sites or tumors are repeatedly remodeled. Many reports have been made on the relationship between SPARC and tumors in various carcinomas, and tumor cells or host stromal cells and inflammatory cells in tumor tissues express SPARC.
  • Ledda et al. Reported in immunohistochemical examination that SPARC expression in human melanoma correlates with tumor progression. (Ledda et al., J. Invest. Delmatol., 108, 210-214, 1997). Ledda et al. Also found that when SPARC antisense expression vectors were used to suppress S PARC expression in human melanoma cells, adhesion and invasiveness were lost in vitro and carcinogenicity was lost in vivo. (Ledda et al., Nature Med., 3, 171-176, 1997).
  • a tumor marker for melanoma serum LDH and 5-S-cysteinyldopa (5-S-CD) widely used in Japan, and more recently, a more sensitive marker, S-1 00 ⁇ protein and melanoma inhibitory activity (MIA), but none of the tumor markers are positive unless they are highly advanced, such as Stage IV.
  • S-1 00 ⁇ protein and melanoma inhibitory activity MIA
  • An object of the present invention is to find another tumor marker useful for early diagnosis of melanoma, and to provide a diagnostic kit and diagnostic method for malignant melanoma using the same.
  • soluble GPC3 protein can be detected in the serum of patients with hepatocellular carcinoma and melanoma, and can be a new tumor marker for hepatocellular carcinoma and melanoma.
  • the present inventors have now discovered that soluble SPARC protein is detected in the serum and plasma of melanoma patients in the same manner as GPC3 and can be a novel tumor marker for melanoma.
  • SPARC protein was able to detect early melanoma as well as GPC3, and by using GPC3 measurement, the diagnosis rate of melanoma could be increased to 60%.
  • a diagnostic kit for malignant melanoma comprising an antibody against SPARC and an antibody against GPC3.
  • a method for diagnosing malignant melanoma comprising measuring SPARC and GPC3 in a sample.
  • the present inventors used the method described in Nakatsura, T. et al., Clin. Cancer Res. 10,6612- 6621, 2004, and combined force of SPARC and GPC3 Serum tumor useful for early diagnosis of ranoma I found out that it was a marker.
  • the amino acid sequence of the human SPARC protein is known, for example, registered as Accession No. NM003118 in the GenBank protein database, and can be easily obtained by those skilled in the art.
  • amino acid sequence of human GPC3 protein is known and can be easily obtained by those skilled in the art.
  • the present invention relates to a malignant melanoma comprising an antibody against SPARC and an antibody against GPC3.
  • the antibody against SPARC and the antibody against GPC3 used in the present invention may be either a polyclonal antibody or a monoclonal antibody, and are known to those skilled in the art (for example, “Neurochemistry Experiment Course 1, Protein 1,389-406, Tokyo Chemical Dojin”). For example).
  • the SPARC protein and GPC3 protein have the known amino acid sequences as described above, and can be produced using conventional protein expression techniques based on the amino acid sequences, and are commercially available (Zymed Laboratori es, CA). ) Can also be used.
  • SDS-OutTM sodium Dodecyl Sulfate Precipitation Reagent; purchased from PIERCE, Rockford, IL
  • the partial peptide of SPARC or GPC3 can be produced by selecting an appropriate partial sequence from the amino acid sequence of SPARC or GPC3 and using ordinary peptide synthesis techniques.
  • an appropriate amount of SPARC protein or GPC3 protein or a partial peptide thereof is administered to an animal such as a rabbit, a guinea pig, a mouse, or a rabbit.
  • Administration may be with an adjuvant (FIA or FCA) that promotes antibody production.
  • FAA or FCA adjuvant
  • the antibody titer can be increased by performing multiple immunizations.
  • antiserum can be obtained by collecting blood from the immunized animal. For example, ammonium sulfate precipitation, fractionation by anion chromatography, or protein A or fixed antigen antigen Polyclonal antibodies can be prepared by performing tea purification.
  • monoclonal antibodies against SPARC or GPC3 are prepared by, for example, immunizing animals with SPA RC protein or GPC3 protein or a partial peptide thereof in the same manner as described above, and then spleen or lymph from this immunized animal after final immunization. Collect a node.
  • the antibody-producing cells and myeloma cells contained in this spleen or lymph node are fused using polyethylene glycol or the like to prepare a hyperidoma.
  • a desired hyperidoma is screened and cultured, and a monoclonal antibody can be prepared from the culture supernatant.
  • the monoclonal antibody can be purified by, for example, ammonium sulfate precipitation, fractionation by anion chromatography, or affinity purification using protein A or immobilized antigen.
  • the antibody may recognize any epitope of SPARC or GPC3.
  • the antibody against SPARC or the antibody against GPC3 is preferably a human type antibody or a human antibody.
  • the human antibody is, for example, a mouse-human chimeric antibody, a mouse cell force antibody gene that produces an antibody against the SPARC protein or GPC3 protein is isolated, and the H chain constant region is recombined with the H chain E H chain constant region gene.
  • a human antibody can be prepared by immunizing a mouse in which the immune system is replaced with a human by SPARC protein or GPC3 protein.
  • the antibody against SPARC and the antibody against GPC3 can be used at a concentration of, for example, 0.5 g / ml, although not limited thereto.
  • the diagnostic kit of the present invention can appropriately contain a pharmaceutically acceptable carrier and the like as necessary.
  • the present invention further provides a method for diagnosing malignant melanoma, which comprises measuring SPARC and GPC3 in a sample.
  • SPARC and GPC3 in a sample can be measured by the step of bringing the sample into contact with an antibody against SPARC and the step of bringing the sample into contact with an antibody against GPC3.
  • the sample include serum, saliva, urine and the like obtained from the subject who may suffer from melanoma, particularly preferably serum.
  • the contact between the sample and the antibody is not particularly limited as long as it is performed based on a method commonly used in the art.
  • Diagnosis includes, for example, specific binding between SPARC and an antibody that may be present in a sample after contact between the sample and the antibody, and specific binding between GPC3 and an antibody that may be present in the sample. Or by using a secondary antibody labeled with a luminescent substance, an enzyme, or the like for quantitative detection. Further, a reaction for diagnosis may be performed in a liquid phase such as a well, or may be performed on a solid support on which an antibody against SPARC or an antibody against GPC3 is immobilized.
  • Specific examples of a method for immunologically detecting SPARC and GPC3 in a sample using an antibody against SPARC and an antibody against GPC3 include an enzyme immunoassay (EIA) such as a sandwich ELISA, or a radioimmunoassay. Law (RIA), etc., and these techniques are well known to those skilled in the art.
  • EIA enzyme immunoassay
  • sandwich ELISA two types of antibodies with different antigen recognition sites are prepared, and one antibody is adsorbed on a plate. The sample is brought into contact with the plate for reaction, the other antibody with a different antigen recognition site is reacted, and an anti-immunoglobin antibody labeled with an enzyme such as peroxidase or alkaline phosphatase is reacted.
  • the SPARC and GPC3 in the sample can be detected or measured by measuring the color intensity with a spectrophotometer.
  • a radioimmunoassay method an antibody labeled with a radioactive substance such as 25 I is used to perform the same operation as the enzyme immunoassay method, and the radiation is measured with a scintillation counter.
  • the diagnostic method of the present invention can be used for diagnosing whether or not the patient has melanoma, and can also be performed over time to confirm the effect of treatment on melanoma.
  • the kit of the present invention contains the above-mentioned antibody against SPARC and antibody against GPC3.
  • at least a reagent necessary for detecting SPARC and GPC3 in the sample for example, a secondary antibody, a coloring reagent, a buffer, etc.
  • a reagent necessary for detecting SPARC and GPC3 in the sample for example, a secondary antibody, a coloring reagent, a buffer, etc.
  • the present invention will be further described with reference to examples. However, the present invention is not limited to these examples.
  • the mouse cell lines B16, B16F1, B16F10, EL4 MCA, and LLC were obtained from Tohoku University Institute of Aging Medicine, Medical Cell Resource Center.
  • RT-PCR was performed according to a known method (for example, Nakatsura, T. et al., Biochem. Biophys. Res. Commun. 281, 936-944, 2001).
  • a mouse SPARC gene-specific PCR primer that amplifies a 533 bp fragment is designed and used to perform RT-PCR with an initial denaturation of 94 ° C, 5 min, and 30 amplification cycles at an annealing temperature of 58 ° C. Reaction was performed.
  • the SPARC PCR primer sequence used was
  • Antisense 5′-AAGCACAGAGTCTGGGTGAGTG-3 ′ (SEQ ID NO: 2).
  • lane 1 B16
  • lane 2 B16-F1
  • lane 3 B16-F10
  • lane 4 MCA
  • lane 5 NIH-3T3
  • lane 6 LLC
  • lane 7 EL4
  • RT-PCR Reverse transcription-PCR
  • the melanoma cell lines G361, CRL1579, SK-MEL-28, and HMV-I were obtained from Tohoku University Research Center for Aging Medicine. 526mel and 888mel were provided by Dr. Y. Kawakami from Keio University. 164, SK-MEL-19, HM3KO, MEWO, colo38 were provided by Dr. T. Kageshita of Kumamoto University.
  • normal human epidermal melanocytes NHEM Purchased from Rabo (Kurashiki Spinning Co., Ltd.).
  • RT-PCR was performed according to a known method (for example, Nakatsura, T. et al., Biochem. Biophys. Res. Commun. 281, 936-944 (2001)).
  • a human SPARC gene-specific PCR primer that amplifies a 343 bp fragment was designed and used to perform an RT-PCR reaction consisting of 26 amplification cycles at 94 ° C, 5 minutes of initial denaturation, and an annealing temperature of 58 ° C. Went.
  • the SPA RC PCR primer sequence used was
  • Antisense 5′-GGTTGTTGTCCTCATCCCTCTCATAC-3 ′ (SEQ ID NO: 4), and ⁇ -endoctin PCR primer sequence for the control experiment is
  • Antisense 5'-GGATCTTC ATGAGGTAGTC AGTC-3 '(SEQ ID NO: 6).
  • lane 1 nevi
  • lane 2 patient 1 (terminal mole type) normal skin
  • lane 3 patient 1 spot
  • lane 4 patient 1 melanoma
  • lane 5 patient 2 (terminal mole type) normal skin
  • Lane 6 Patient 2 plaques
  • Lane 7 Patient 2 melanoma
  • Lane 8 Patient 3 (superficial enlarged) Melanoma
  • Lane 9 Patient 4 (superficial enlarged) normal skin
  • Lane 10 Patient 4 ( Superficial enlargement) Group
  • lane 11 Patient 4 (superficial enlargement) melanoma
  • Lane 12 Patient 5 (superficial enlargement) melanoma metastasis.
  • the SPARC protein was only expressed in the maternal, normal skin and plaques, but the SPARC protein was highly expressed in all melanoma tissues.
  • a 96-well ELISA plate (Nunc, Denmark) was coated at room temperature with 0.05 ⁇ g Z Wenore anti-human SPARC monochrome-nanore antibody (Zymed laboratories, San Francisco) in PBS, pH 7.4. Subsequently, the plate was blocked using 100% Block Ace (Dainippon Pharmaceutical Co., Ltd.) at room temperature for 1 hour. Positive control standard sample and culture supernatant, patient serum diluted 200-fold with 10% Block Ace was added with piotin-anti-human SPARC polyclonal antibody (R & D system, minneapolis) and incubated at room temperature for 2 hours .
  • the average value of melanoma patients is 606 ng / ml
  • the average value of healthy individuals who are positive in 4 of 11 (36.4%) is 140 ng / ml.
  • One in 21 was positive and the specificity was 95%.
  • SPARC protein was detected in melanoma patient serum by melanoma macroscopic classification. The results are shown in Table 3. SPARC showed an increase in protein in various tissue types, regardless of the melanoma tissue type.
  • the diagnostic kit and diagnostic method according to the present invention are very useful for diagnosing whether or not a melanoma is affected.
  • the combination of SPARC and GPC3 has proven very useful for applications in cancer diagnosis for many melanoma patients worldwide.
  • FIG. 1 shows the expression of SPARC mRNA.
  • FIG. 2 shows the expression of SPARC protein in human melanoma yarn and weave by Western blotting.
  • FIG. 3 shows the results of quantification by ELISA of GPC3 protein secreted into the culture supernatant of melanoma cell lines.
  • FIG. 4 shows the presence of soluble SPARC protein in the serum of melanoma patients.
  • FIG. 5 shows the presence of soluble SPARC protein in the serum of melanoma patients by stage.
  • FIG. 5 shows the presence of soluble SPARC protein in the plasma of melanoma patients.

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PCT/JP2005/014567 2004-10-19 2005-08-09 悪性黒色腫（メラノーマ）の新規な診断キット WO2006043362A1 (ja)

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Application Number Priority Date Filing Date Title
US11/577,435 US8017345B2 (en) 2004-10-19 2005-08-09 Diagnostic kit for malignant melanoma
DE602005016831T DE602005016831D1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 2004-10-19 2005-08-09
EP05770440A EP1813943B1 (en) 2004-10-19 2005-08-09 Novel diagnostic kit for malignant melanoma
AU2005297303A AU2005297303B2 (en) 2004-10-19 2005-08-09 Novel diagnostic kit for malignant melanoma
JP2006542257A JP4834839B2 (ja) 2004-10-19 2005-08-09 悪性黒色腫（メラノーマ）の新規な診断キット

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007145318A1 (ja) * 2006-06-16 2007-12-21 Kumamoto University Sparc由来の癌拒絶抗原ペプチド及びこれを含む医薬
CN102576016A (zh) * 2009-09-18 2012-07-11 阿布拉西斯生物科学有限责任公司 Sparc微环境标签在癌症治疗中的应用
WO2013191146A1 (ja) 2012-06-18 2013-12-27 独立行政法人国立がん研究センター 悪性黒色腫（メラノーマ）の診断キット
US9193782B2 (en) 2010-06-03 2015-11-24 Abraxis Bioscience, Llc Use of the SPARC microenvironment signature in the treatment of cancer

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2006277295B2 (en) 2005-08-09 2011-08-11 Oncotherapy Science, Inc. Glypican-3 (GPC3)-derived tumor rejection antigenic peptides useful for HLA-A2-positive patients and pharmaceutical comprising the same
EP2294216A4 (en) 2008-05-14 2011-11-23 Dermtech Int DIAGNOSIS OF MELANOMA AND SOLAR LENTIGO BY ANALYSIS OF NUCLEIC ACIDS
EP2376534A4 (en) * 2008-12-05 2012-05-30 Abraxis Bioscience Llc SPARC-BINDING ScFc
EP3085387A1 (en) * 2010-04-26 2016-10-26 Abraxis BioScience, LLC Sparc binding antibodies and uses thereof
US20130281376A1 (en) * 2010-10-08 2013-10-24 Abraxis Bioscience, Llc Sparc microenvironment signature, plasma sparc, and ldh as prognostic biomarkers in the treatment of cancer
US20140314697A1 (en) * 2013-04-18 2014-10-23 Corum Inc. Method for Inhibiting Inflammation and Reducing Melanophilin Expression with Glycine Derivatives And the Composition Thereof
US20150005184A1 (en) * 2013-06-28 2015-01-01 Dermtech International Diagnosis of melanoma by nucleic acid analysis
CA3090785A1 (en) 2018-02-14 2019-08-22 John Daniel Dobak Iii Novel gene classifiers and uses thereof in non-melanoma skin cancers
EP3948290A4 (en) 2019-03-26 2023-08-09 Dermtech, Inc. NEW GENE CLASSIFIERS AND THEIR USES FOR SKIN CANCERS

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003528564A (ja) 1998-06-06 2003-09-30 ジェノスティック ファーマ リミテッド 遺伝的プロファイリングに使用するプローブ
AU2003281325A1 (en) * 2002-07-02 2004-01-23 The Johns Hopkins University Secreted and cytoplasmic tumor endothelial markers
US20060251666A1 (en) 2002-08-30 2006-11-09 Tetsuya Nakatsura Cancer antigens and utilization thereof
EP2325338B1 (en) * 2003-07-17 2015-01-21 Pacific Edge Limited Markers for detection of gastric cancer
US7803533B2 (en) 2003-10-29 2010-09-28 Kumamoto Technology & Industry Foundation Diagnostic agent for malignant melanoma

Non-Patent Citations (13)

* Cited by examiner, † Cited by third party
Title
"Protein I", TOKYO KAGAKU DOZIN CO., LTD., article "New Biochemical Experiment 1 (Shin-Seikagaku Jikken Ko-za 1)", pages: 389 - 406
BRADSHAW; SAGE, J. CLIN. INVEST, vol. 107, 2001, pages 1049 - 1054
BREKKEN; SAGE, MATRIX BIOL., vol. 19, 2001, pages 816 - 827
LEDDA ET AL., J. INVEST. DELMATOL., vol. 108, 1997, pages 210 - 214
LEDDA ET AL., NATURE MED., vol. 3, 1997, pages 171 - 176
LEDDA ET AL: "The Expression of the SPARC Is Associated with the Neoplastic Progression of Human Melonoma.", THE JOURNAL OF INVESTIGATIVE DERMATOLOGY., vol. 108, no. 2, 1997, pages 210 - 214, XP002991375 *
MANN K ET AL., FASEB J, vol. 218, 1987, pages 167 - 172
NAKATSURA ET AL: "Identification of Glypican-3 as a Novel Tumor Marker for Melanoma.", CLINICAL CANCER RESEARCH., vol. 10, no. 19, 1 October 2004 (2004-10-01), pages 6612 - 6621, XP002991376 *
NAKATSURA T. ET AL., BIOCHEM. BIOPHYS. RES. COMMUN., vol. 281, 2001, pages 936 - 944
NAKATSURA T. ET AL., BIOCHEM. BIOPHYS. RES. COMMUN., vol. 306, 2003, pages 16 - 25
NAKATSURA, T. ET AL., CLIN. CANCER RES., vol. 10, 2004, pages 6612 - 6621
See also references of EP1813943A4
TERMINE JD ET AL., CELL, vol. 26, September 1981 (1981-09-01), pages 99 - 105

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9120842B2 (en) 2006-06-16 2015-09-01 Onco Therapy Science, Inc. SPARC-derived tumor rejection antigenic peptides and medicaments comprising the same
CN105418751A (zh) * 2006-06-16 2016-03-23 肿瘤疗法·科学股份有限公司 来自sparc的癌排斥抗原肽以及含有该肽的药物
AU2007259667B2 (en) * 2006-06-16 2012-06-14 Oncotherapy Science, Inc. SPARC-derived tumor rejection antigenic peptides and medicaments comprising the same
JP5150849B2 (ja) * 2006-06-16 2013-02-27 オンコセラピー・サイエンス株式会社 Ｓｐａｒｃ由来の癌拒絶抗原ペプチド及びこれを含む医薬
US8470968B2 (en) 2006-06-16 2013-06-25 Onco Therapy Science, Inc. SPARC-derived tumor rejection antigenic peptides and medicaments comprising the same
US8053557B2 (en) 2006-06-16 2011-11-08 Onco Therapy Science, Inc. SPARC-derived tumor rejection antigenic peptides and medicaments comprising the same
KR101408173B1 (ko) 2006-06-16 2014-06-16 온코세라피 사이언스 가부시키가이샤 Ｓｐａｒｃ 유래의 암 거절항원 펩티드 및 이를 포함하는 의약
CN103435683A (zh) * 2006-06-16 2013-12-11 肿瘤疗法·科学股份有限公司 来自sparc的癌排斥抗原肽以及含有该肽的药物
WO2007145318A1 (ja) * 2006-06-16 2007-12-21 Kumamoto University Sparc由来の癌拒絶抗原ペプチド及びこれを含む医薬
CN105418751B (zh) * 2006-06-16 2019-03-05 肿瘤疗法·科学股份有限公司 来自sparc的癌排斥抗原肽以及含有该肽的药物
CN103435683B (zh) * 2006-06-16 2016-02-03 肿瘤疗法·科学股份有限公司 来自sparc的癌排斥抗原肽以及含有该肽的药物
CN102576016A (zh) * 2009-09-18 2012-07-11 阿布拉西斯生物科学有限责任公司 Sparc微环境标签在癌症治疗中的应用
US9193782B2 (en) 2010-06-03 2015-11-24 Abraxis Bioscience, Llc Use of the SPARC microenvironment signature in the treatment of cancer
US9465030B2 (en) 2012-06-18 2016-10-11 National Cancer Center Kit for diagnosing malignant melanoma
WO2013191146A1 (ja) 2012-06-18 2013-12-27 独立行政法人国立がん研究センター 悪性黒色腫（メラノーマ）の診断キット

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AU2005297303B2 (en) 2011-11-10
EP1813943A4 (en) 2007-12-12
EP1813943B1 (en) 2009-09-23
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