JP6707505B2 - 腫瘍細胞を検出するためのステロイド受容体アッセイ - Google Patents
腫瘍細胞を検出するためのステロイド受容体アッセイ Download PDFInfo
- Publication number
- JP6707505B2 JP6707505B2 JP2017207034A JP2017207034A JP6707505B2 JP 6707505 B2 JP6707505 B2 JP 6707505B2 JP 2017207034 A JP2017207034 A JP 2017207034A JP 2017207034 A JP2017207034 A JP 2017207034A JP 6707505 B2 JP6707505 B2 JP 6707505B2
- Authority
- JP
- Japan
- Prior art keywords
- tumor cells
- circulating tumor
- antibody
- product
- sample
- 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.)
- Active
Links
- 210000004881 tumor cell Anatomy 0.000 title claims description 4
- 108010085012 Steroid Receptors Proteins 0.000 title description 17
- 102000005969 steroid hormone receptors Human genes 0.000 title description 17
- 238000003556 assay Methods 0.000 title description 3
- 208000005443 Circulating Neoplastic Cells Diseases 0.000 claims description 54
- 238000000034 method Methods 0.000 claims description 36
- 239000000523 sample Substances 0.000 claims description 35
- 210000004027 cell Anatomy 0.000 claims description 34
- 239000012472 biological sample Substances 0.000 claims description 22
- 102000015694 estrogen receptors Human genes 0.000 claims description 20
- 108010038795 estrogen receptors Proteins 0.000 claims description 20
- 239000003153 chemical reaction reagent Substances 0.000 claims description 18
- 210000004369 blood Anatomy 0.000 claims description 15
- 239000008280 blood Substances 0.000 claims description 15
- 239000002245 particle Substances 0.000 claims description 15
- 238000004458 analytical method Methods 0.000 claims description 14
- 239000003446 ligand Substances 0.000 claims description 12
- 210000004899 c-terminal region Anatomy 0.000 claims description 11
- 210000004897 n-terminal region Anatomy 0.000 claims description 11
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 claims description 8
- 210000005266 circulating tumour cell Anatomy 0.000 claims description 8
- 239000013610 patient sample Substances 0.000 claims description 8
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000007850 fluorescent dye Substances 0.000 claims description 7
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 claims description 6
- 210000001185 bone marrow Anatomy 0.000 claims description 6
- 238000010191 image analysis Methods 0.000 claims description 6
- 238000012360 testing method Methods 0.000 claims description 6
- 230000005291 magnetic effect Effects 0.000 claims description 5
- 238000012216 screening Methods 0.000 claims description 4
- 206010055113 Breast cancer metastatic Diseases 0.000 claims description 3
- 238000004163 cytometry Methods 0.000 claims description 3
- 238000000684 flow cytometry Methods 0.000 claims description 3
- 238000010820 immunofluorescence microscopy Methods 0.000 claims description 3
- 208000037819 metastatic cancer Diseases 0.000 claims description 3
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims description 3
- 230000003595 spectral effect Effects 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims 8
- 238000012921 fluorescence analysis Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000306 component Substances 0.000 description 12
- 206010006187 Breast cancer Diseases 0.000 description 6
- 208000026310 Breast neoplasm Diseases 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 108010007005 Estrogen Receptor alpha Proteins 0.000 description 4
- 102100038595 Estrogen receptor Human genes 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 102000011782 Keratins Human genes 0.000 description 3
- 108010076876 Keratins Proteins 0.000 description 3
- 108010004729 Phycoerythrin Proteins 0.000 description 3
- 206010036790 Productive cough Diseases 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 210000003802 sputum Anatomy 0.000 description 3
- 208000024794 sputum Diseases 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 102000000905 Cadherin Human genes 0.000 description 2
- 108050007957 Cadherin Proteins 0.000 description 2
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 2
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 2
- 230000010100 anticoagulation Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 238000007885 magnetic separation Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 102000003998 progesterone receptors Human genes 0.000 description 2
- 108090000468 progesterone receptors Proteins 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- YQNRVGJCPCNMKT-LFVJCYFKSA-N 2-[(e)-[[2-(4-benzylpiperazin-1-ium-1-yl)acetyl]hydrazinylidene]methyl]-6-prop-2-enylphenolate Chemical compound [O-]C1=C(CC=C)C=CC=C1\C=N\NC(=O)C[NH+]1CCN(CC=2C=CC=CC=2)CC1 YQNRVGJCPCNMKT-LFVJCYFKSA-N 0.000 description 1
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 1
- 102100023126 Cell surface glycoprotein MUC18 Human genes 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 1
- 101000623903 Homo sapiens Cell surface glycoprotein MUC18 Proteins 0.000 description 1
- 101000838335 Homo sapiens Dual specificity protein phosphatase 2 Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 101001080401 Homo sapiens Proteasome assembly chaperone 1 Proteins 0.000 description 1
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 1
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 108010013709 Leukocyte Common Antigens Proteins 0.000 description 1
- 108050000637 N-cadherin Proteins 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229960005552 PAC-1 Drugs 0.000 description 1
- 102100027583 Proteasome assembly chaperone 1 Human genes 0.000 description 1
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 1
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 1
- DPKHZNPWBDQZCN-UHFFFAOYSA-N acridine orange free base Chemical compound C1=CC(N(C)C)=CC2=NC3=CC(N(C)C)=CC=C3C=C21 DPKHZNPWBDQZCN-UHFFFAOYSA-N 0.000 description 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 102000001307 androgen receptors Human genes 0.000 description 1
- 108010080146 androgen receptors Proteins 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 239000012503 blood component Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000005929 chemotherapeutic response Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000011554 ferrofluid Substances 0.000 description 1
- 230000005294 ferromagnetic effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000012151 immunohistochemical method Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 230000005389 magnetism Effects 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000000633 nuclear envelope Anatomy 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- 239000001048 orange dye Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
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
-
- 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
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
- G01N33/54326—Magnetic particles
-
- 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
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
-
- 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
- G01N33/57415—Specifically defined cancers of breast
-
- 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
-
- 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
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
-
- 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
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
- G01N33/743—Steroid hormones
-
- 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
- G01N2333/72—Assays involving receptors, cell surface antigens or cell surface determinants for hormones
- G01N2333/723—Steroid/thyroid hormone superfamily, e.g. GR, EcR, androgen receptor, oestrogen receptor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/54—Determining the risk of relapse
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Chemical & Material Sciences (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Description
a)患者から生物学的試料(血液及び骨髄)を採取する段階と、
b)生物学的試料を循環腫瘍細胞と特異的に反応するリガンドと接触させて他のサンプル成分が実質的に除外されたような、結合された循環腫瘍細胞を生物学的試料の他のサンプル成分から分離させる段階と、
c)段階(b)のサンプルに特異的に結合する少なくとも1種の試薬に、段階(b)のサンプルを接触させる段階と、
d)段階(c)のサンプルを、細胞内のステロイド受容体に対する結合親和力を有する薬剤と接触させる段階と、
e)サンプルを解析して、ステロイド受容体を発現する循環腫瘍細胞の存在を判別する段階と、を含む。
a)循環腫瘍細胞と特異的に反応して他のサンプル成分が実質的に除外されたような、結合された循環腫瘍細胞を生物学的試料の他のサンプル成分から分離させるリガンドと、
b)循環腫瘍細胞及び患者の他のサンプル成分の一方又は両方を特異的に結合する少なくとも1種の試薬と、
c)患者の循環腫瘍細胞においてステロイド受容体に対する結合親和力を有する薬剤と、を含む。
(1) 転移性癌の患者からの循環腫瘍細胞を特徴付ける方法であって、
a)前記患者から生物学的試料(血液及び骨髄)を採取する段階と、
b)他のサンプル成分を実質的に除外して、循環腫瘍細胞と特異的に反応し、そのような結合された循環腫瘍細胞を前記生物学的試料の他のサンプル成分から分離させるリガンドと、前記生物学的試料を接触させる段階と、
c)段階(b)の前記サンプルに特異的に結合する少なくとも1種の試薬に、段階(b)の前記サンプルを接触させる段階と、
d)段階(c)の前記サンプルを、細胞内のステロイド受容体に対する結合親和力を有する薬剤と接触させる段階と、
e)前記サンプルを解析して、ステロイド受容体を発現する循環腫瘍細胞の存在を判別する段階と、
を含む方法。
(2) 前記ステロイド受容体を発現する循環腫瘍細胞の数を特定する段階を更に含む、実施態様1に記載の方法。
(3) 循環腫瘍細胞と特異的に反応する薬剤を、前記循環腫瘍細胞内の前記ステロイド受容体のN末端領域及びC末端領域の一方又は両方に連結する、実施態様1に記載の方法。
(4) 前記試薬がDAPI、サイトケラチン及びCD45陰性(CD45 neg)からなる群より選択される、実施態様1に記載の方法。
(5) 前記リガンドが前記腫瘍細胞上の上皮細胞接着エピトープに特異的に結合する、実施態様1に記載の方法。
(7) 段階(e)の前記サンプルが、マルチパラメーターフローサイトメトリー、免疫蛍光顕微鏡法、レーザー走査サイトメトリー、明視野に基づく画像解析、スペクトル画像解析、手動細胞解析、CELLSTRACKS(登録商標)解析、及び自動細胞解析からなる群から選択される少なくとも1つの方法によって解析される、実施態様1に記載の方法。
(8) 段階(b)の前記生成物を磁場にさらす段階を更に含む、実施態様6に記載の方法。
(9) 前記磁気応答粒子がコロイド状である、実施態様6に記載の方法。
(10) 前記薬剤がID5、CF11、E115(rbモノ)、ER119.3、及びSP−1(rbモノ(rb mono))からなる群より選択される抗体である、実施態様1に記載の方法。
(12) ステロイド受容体を発現する循環腫瘍細胞の存在について、患者サンプルをスクリーニングするための試験キットであって、
a)他のサンプル成分を実質的に除外して、循環腫瘍細胞と特異的に反応して、そのような結合された循環腫瘍細胞を前記生物学的試料の他のサンプル成分から分離させるリガンドと、
b)循環腫瘍細胞及び患者の他のサンプル成分の一方又は両方に特異的に結合する少なくとも1種の試薬と、
c)前記患者の前記循環腫瘍細胞においてステロイド受容体に対する結合親和力を有する薬剤と、
を含む試験キット。
Claims (17)
- 転移性乳癌の患者からの循環腫瘍細胞の特徴付けをするためのキットの製造における成分i)、ii)、及びiii)、
i)抗EpCAM抗体と磁気応答粒子との複合体であって、前記複合体は、生物学的試料中の前記循環腫瘍細胞と特異的に反応して前記生物学的試料の他のサンプル成分を実質的に除外し、結合された前記循環腫瘍細胞を前記生物学的試料の前記他のサンプル成分から分離させる、複合体、
ii)前記患者の前記循環腫瘍細胞及び前記他のサンプル成分の一方又は両方に特異的に結合する少なくとも1種の試薬であって、DAPI、蛍光染料に接合された抗サイトケラチン抗体、およびCD45に特異的に結合する蛍光接合体、からなる群から選択される試薬、及び、
iii)エストロゲン受容体のN末端領域及びC末端領域の一方または両方に対する抗体であって、前記抗体が、H222、ID5、E115(rbモノ)、及びSP−1(rbモノ)からなる群から選択される、抗体、
の使用であって、前記特徴付けは、
(a)血液及び骨髄サンプルから選択された、前記患者からの前記生物学的試料を提供する段階と、
(b)(i)の前記複合体と、前記段階(a)の前記生物学的試料を接触させる段階と、
(c)段階(b)の生成物を磁場にさらして、結合した前記循環腫瘍細胞を前記段階(a)の前記生物学的試料の前記他のサンプル成分から分離し、減少した容積の生成物を得る段階と、
(d)段階(c)の生成物中の前記結合した循環腫瘍細胞を、(ii)の前記少なくとも1種の試薬と接触させる段階と、
(e)段階(d)の生成物中の前記結合した循環腫瘍細胞を、(iii)の前記抗体と接触させる段階と、
(f)前記エストロゲン受容体を発現する前記循環腫瘍細胞の存在を決定するために段階(e)の生成物を解析する段階と、
(g)段階(e)の生成物中の、前記エストロゲン受容体を発現する前記循環腫瘍細胞の数を決定する段階と、を含む、使用。 - 段階(f)における解析は、マルチパラメーターフローサイトメトリー、免疫蛍光顕微鏡法、レーザー走査サイトメトリー、明視野に基づく画像解析、スペクトル画像解析、手動細胞解析、CELLSTRACKS(登録商標)解析、及び自動細胞解析からなる群から選択される少なくとも1つの方法によって行われる、請求項1に記載の使用。
- 前記磁気応答粒子がコロイド状である、請求項1に記載の使用。
- 前記エストロゲン受容体の前記N末端領域及び前記C末端領域の一方または両方に対する抗体は前記E115(rbモノ)である、請求項1に記載の使用。
- 前記抗EpCAM抗体はVU−1D9である、請求項1に記載の使用。
- 前記抗EpCAM抗体であるVU−1D9は前記磁気応答粒子に接合する、請求項5に記載の使用。
- 段階(c)の生成物を、HER/2neuに特異的な抗体と接触させる段階を、段階(d)がさらに含む、請求項1に記載の使用。
- 前記HER/2neuに特異的な抗体が、モノクローナル抗体Her−81である、請求項7に記載の使用。
- エストロゲン受容体を発現する循環腫瘍細胞の存在について、転移性乳癌患者のサンプルをスクリーニングするための試験キットであって、
a)抗EpCAM抗体と磁気応答粒子との複合体であって、前記複合体は前記循環腫瘍細胞と特異的に反応して、患者サンプルの他のサンプル成分を実質的に除外し、結合した循環腫瘍細胞を前記患者サンプルの前記他のサンプル成分から分離させる、複合体、
b)患者の前記循環腫瘍細胞及び前記他のサンプル成分の一方又は両方に特異的に結合する少なくとも1つの試薬であって、DAPI、蛍光染料に接合した抗サイトケラチン抗体、及びCD45に特異的に結合する蛍光接合体からなる群から選択される試薬、及び、
c)前記患者の前記循環腫瘍細胞内の前記エストロゲン受容体のN末端領域及びC末端領域のいずれか一方又は両方に対する抗体であって、H222、ID5、E115(rbモノ)、及びSP−1(rbモノ)からなる群から選択される抗体を含む、試薬キット。 - 転移性癌の患者からの循環腫瘍細胞を特徴付けるためのin vitro方法であって、
(a)血液及び骨髄サンプルから選択された、前記患者からの生物学的試料を提供する段階と、
(b)前記生物学的試料を前記循環腫瘍細胞と特異的に反応するリガンドと接触させて、前記生物学的試料の前記循環腫瘍細胞以外のサンプル成分を実質的に排除して、結合した前記循環腫瘍細胞を前記生物学的試料の前記循環腫瘍細胞以外の前記サンプル成分から分離させる段階であって、前記リガンドは、磁気応答粒子に接合した抗EpCAM抗体である、段階と、
(c)段階(b)の生成物を磁場にさらし、結合した前記循環腫瘍細胞を含む、減少した容積の生成物を得る段階と、
(d)段階(c)の生成物中の前記循環腫瘍細胞を、段階(b)の生成物中の前記循環腫瘍細胞に特異的に結合する少なくとも1種の試薬と接触させる段階であって、前記少なくとも1種の試薬は、DAPI、蛍光染料に接合した抗サイトケラチン抗体、及びCD45に特異的に結合する蛍光接合体からなる群から選択される、段階と、
(e)段階(d)の生成物中の前記循環腫瘍細胞を、エストロゲン受容体のN末端領域及びC末端領域の一方又は両方に対する結合親和力を有する薬剤と接触させる段階であって、前記薬剤が、H222、ID5、E115(rbモノ)、及びSP−1(rbモノ)からなる群から選択される段階と、
(f)前記エストロゲン受容体を発現する前記循環腫瘍細胞の存在を決定するために段階(e)の生成物を解析する段階と、
(g)段階(e)の生成物中における前記エストロゲン受容体を発現する前記循環腫瘍細胞の数を決定する段階と、を含むin vitro方法。 - 段階(f)における解析は、マルチパラメーターフローサイトメトリー、免疫蛍光顕微鏡法、レーザー走査サイトメトリー、明視野に基づく画像解析、スペクトル画像解析、手動細胞解析、免疫磁気的に選択された循環腫瘍細胞(CTC)の計数のための半自動蛍光解析、及び自動細胞解析からなる群から選択される少なくとも1つの方法によって行われる、請求項10に記載のin vitro方法。
- 前記磁気応答粒子がコロイド状である、請求項10に記載のin vitro方法。
- 前記エストロゲン受容体の前記N末端領域及び前記C末端領域の一方または両方に対する結合親和力を有する前記薬剤は前記E115(rbモノ)である、請求項10に記載のin vitro方法。
- 前記抗EpCAM抗体はVU−1D9である、請求項10に記載のin vitro方法。
- 前記抗EpCAM抗体であるVU−1D9は前記磁気応答粒子に接合する、請求項10に記載のin vitro方法。
- 段階(c)の生成物を、HER/2neuに特異的な抗体と接触させる段階を、段階(d)がさらに含む、請求項10に記載のin vitro方法。
- 前記HER/2neuに特異的な抗体が、モノクローナル抗体Her−81である、請求項16に記載のin vitro方法。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161470618P | 2011-04-01 | 2011-04-01 | |
US61/470,618 | 2011-04-01 | ||
US13/432,248 | 2012-03-28 | ||
US13/432,248 US20120252038A1 (en) | 2011-04-01 | 2012-03-28 | Steroid receptor assays |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014502816A Division JP2014513283A (ja) | 2011-04-01 | 2012-03-30 | 腫瘍細胞を検出するためのステロイド受容体アッセイ |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2018021934A JP2018021934A (ja) | 2018-02-08 |
JP2018021934A5 JP2018021934A5 (ja) | 2018-03-22 |
JP6707505B2 true JP6707505B2 (ja) | 2020-06-10 |
Family
ID=46927724
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014502816A Pending JP2014513283A (ja) | 2011-04-01 | 2012-03-30 | 腫瘍細胞を検出するためのステロイド受容体アッセイ |
JP2017207034A Active JP6707505B2 (ja) | 2011-04-01 | 2017-10-26 | 腫瘍細胞を検出するためのステロイド受容体アッセイ |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014502816A Pending JP2014513283A (ja) | 2011-04-01 | 2012-03-30 | 腫瘍細胞を検出するためのステロイド受容体アッセイ |
Country Status (20)
Country | Link |
---|---|
US (1) | US20120252038A1 (ja) |
EP (1) | EP2694971B1 (ja) |
JP (2) | JP2014513283A (ja) |
KR (1) | KR20140019823A (ja) |
CN (1) | CN103608681A (ja) |
BR (1) | BR112013025287A2 (ja) |
CA (1) | CA2831567A1 (ja) |
CY (1) | CY1123191T1 (ja) |
DK (1) | DK2694971T3 (ja) |
ES (1) | ES2793485T3 (ja) |
HR (1) | HRP20200860T1 (ja) |
HU (1) | HUE050711T2 (ja) |
IL (1) | IL228564B (ja) |
LT (1) | LT2694971T (ja) |
MX (1) | MX360225B (ja) |
PL (1) | PL2694971T3 (ja) |
PT (1) | PT2694971T (ja) |
RS (1) | RS60678B1 (ja) |
SI (1) | SI2694971T1 (ja) |
WO (1) | WO2012135560A1 (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10253107B2 (en) * | 2012-10-26 | 2019-04-09 | The University Of Queensland | Use of endocytosis inhibitors and antibodies for cancer therapy |
CN109975097A (zh) * | 2019-04-18 | 2019-07-05 | 山东师范大学 | 一种基于适配体的肿瘤细胞染色探针组合 |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5292638A (en) * | 1990-12-07 | 1994-03-08 | The Regents Of The University Of California | Method of determining functional estrogen receptors for prognosis of cancer |
CA2077781A1 (en) * | 1991-09-23 | 1993-03-24 | James W. Bacus | Method and apparatus for automated assay of biological specimens |
WO1997046882A1 (en) | 1996-06-07 | 1997-12-11 | Immunivest Corporation | Magnetic separation employing external and internal gradients |
EP1062515B1 (en) * | 1998-02-12 | 2009-11-25 | Immunivest Corporation | Methods and reagents for the rapid and efficient isolation of circulating cancer cells |
BR0207290A (pt) * | 2001-02-16 | 2005-06-07 | Immunivest Corp | Método para analisar um paciente quanto à presença de uma malignidade, célula maligna isolada das células cultivadas, vacina de tumor, molécula associada com diátese de tumor alterada, métodos para determinar alterações em moléculas associadas com diátese de tumor como um meio para predizer a eficácia da terapia, como um meio para analisar dosagem apropriada para terapia, como um meio para monitorar eficácia da terapia, como um meio para analisar progressão de câncer, para realizar uma biópsia de corpo inteiro em um paciente, e para identificar alterações em uma célula de tumor circulante relativamente a células presentes numa massa de tumor in situ, e, kit de teste para analisar uma amostra de paciente quanto à presença de uma célula maligna não-hematopoiética |
IL160210A0 (en) * | 2001-08-23 | 2004-07-25 | Immunivest Corp | Stabilization of cells and biological specimens for analysis |
KR20040047971A (ko) * | 2001-10-26 | 2004-06-05 | 이뮤니베스트 코포레이션 | 동일 샘플상에서의 광범위 핵산 및 이의 형태학적 특질에대한 다중 매개변수 분석법 |
CN1871517A (zh) * | 2002-02-19 | 2006-11-29 | 免疫公司 | 快速有效分离循环癌细胞的方法和试剂 |
US7011794B2 (en) | 2002-11-25 | 2006-03-14 | Immunivest Corporation | Upon a cartridge for containing a specimen sample for optical analysis |
US20040171091A1 (en) * | 2003-02-27 | 2004-09-02 | Cell Work, Inc. | Standardized evaluation of therapeutic efficacy based on cellular biomarkers |
CA2516795C (en) * | 2003-02-27 | 2013-01-15 | Immunivest Corporation | Circulating tumor cells (ctc's): early assessment of time to progression,_survival and response to therapy in metastatic cancer patients |
CA2647743A1 (en) * | 2006-04-18 | 2007-10-25 | Wellstat Biologics Corporation | Detection of steroid receptors on circulating carcinoma cells and treatment |
JP5350369B2 (ja) * | 2007-05-31 | 2013-11-27 | ダコ デンマーク アクティーゼルスカブ | 乳癌治療および予後におけるesrコピー数変化の利用方法 |
US20090061456A1 (en) * | 2007-08-30 | 2009-03-05 | Allard William J | Method for predicting progression free and overall survival at each follow-up time point during therapy of metastatic breast cancer patients using circulating tumor cells |
US8071395B2 (en) * | 2007-12-12 | 2011-12-06 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and apparatus for magnetic separation of cells |
JP2010151678A (ja) * | 2008-12-25 | 2010-07-08 | Olympus Corp | 大腸癌の診断方法および大腸癌診断用キット |
WO2011002649A1 (en) * | 2009-06-30 | 2011-01-06 | Veridex, Llc | Analysis of circulating tumor-related microparticles |
EP3306321A1 (en) * | 2010-07-07 | 2018-04-11 | The Regents of The University of Michigan | Diagnosis and treatment of breast cancer |
-
2012
- 2012-03-28 US US13/432,248 patent/US20120252038A1/en not_active Abandoned
- 2012-03-30 CA CA2831567A patent/CA2831567A1/en not_active Abandoned
- 2012-03-30 PT PT127168250T patent/PT2694971T/pt unknown
- 2012-03-30 BR BR112013025287A patent/BR112013025287A2/pt not_active IP Right Cessation
- 2012-03-30 SI SI201231787T patent/SI2694971T1/sl unknown
- 2012-03-30 HU HUE12716825A patent/HUE050711T2/hu unknown
- 2012-03-30 JP JP2014502816A patent/JP2014513283A/ja active Pending
- 2012-03-30 MX MX2013011428A patent/MX360225B/es active IP Right Grant
- 2012-03-30 PL PL12716825T patent/PL2694971T3/pl unknown
- 2012-03-30 RS RS20200616A patent/RS60678B1/sr unknown
- 2012-03-30 CN CN201280016743.7A patent/CN103608681A/zh active Pending
- 2012-03-30 KR KR1020137028837A patent/KR20140019823A/ko not_active Application Discontinuation
- 2012-03-30 WO PCT/US2012/031338 patent/WO2012135560A1/en active Application Filing
- 2012-03-30 EP EP12716825.0A patent/EP2694971B1/en active Active
- 2012-03-30 LT LTEP12716825.0T patent/LT2694971T/lt unknown
- 2012-03-30 ES ES12716825T patent/ES2793485T3/es active Active
- 2012-03-30 DK DK12716825.0T patent/DK2694971T3/da active
-
2013
- 2013-09-29 IL IL228564A patent/IL228564B/en active IP Right Grant
-
2017
- 2017-10-26 JP JP2017207034A patent/JP6707505B2/ja active Active
-
2020
- 2020-05-28 HR HRP20200860TT patent/HRP20200860T1/hr unknown
- 2020-05-29 CY CY20201100488T patent/CY1123191T1/el unknown
Also Published As
Publication number | Publication date |
---|---|
DK2694971T3 (da) | 2020-06-02 |
HRP20200860T1 (hr) | 2020-09-04 |
CN103608681A (zh) | 2014-02-26 |
KR20140019823A (ko) | 2014-02-17 |
BR112013025287A2 (pt) | 2017-11-14 |
EP2694971B1 (en) | 2020-03-04 |
IL228564A0 (en) | 2013-12-31 |
PT2694971T (pt) | 2020-06-16 |
LT2694971T (lt) | 2020-08-10 |
JP2014513283A (ja) | 2014-05-29 |
US20120252038A1 (en) | 2012-10-04 |
PL2694971T3 (pl) | 2020-11-02 |
MX2013011428A (es) | 2014-06-23 |
CA2831567A1 (en) | 2012-10-04 |
SI2694971T1 (sl) | 2020-09-30 |
HUE050711T2 (hu) | 2020-12-28 |
ES2793485T3 (es) | 2020-11-16 |
JP2018021934A (ja) | 2018-02-08 |
CY1123191T1 (el) | 2021-10-29 |
RS60678B1 (sr) | 2020-09-30 |
EP2694971A1 (en) | 2014-02-12 |
IL228564B (en) | 2018-08-30 |
MX360225B (es) | 2018-10-25 |
WO2012135560A1 (en) | 2012-10-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5479355B2 (ja) | 血液中の循環黒色腫細胞の自動計数及び特徴付け | |
JP6254951B2 (ja) | 哺乳類の対象における5t4陽性循環腫瘍細胞を検出するための方法および5t4陽性がんの診断の方法 | |
TWI577389B (zh) | 使用多專一性捕捉及雞尾酒檢測試劑檢測胰臟病患之循環腫瘤細胞的方法及套組 | |
JP2014521958A (ja) | 胸腔内液若しくは漿液と関連する腫瘍細胞の特徴づけによる癌の診断方法 | |
US20140113310A9 (en) | Cancer detection markers | |
WO2010065968A1 (en) | Cancer detection markers | |
JP7026957B2 (ja) | 循環癌関連マクロファージ様細胞(caml)を使用して癌を有する被験体における全生存期間及び無増悪生存期間を予測する方法 | |
US6828157B1 (en) | Products and methods for single parameter and multiparameter phenotyping of cells | |
JP6707505B2 (ja) | 腫瘍細胞を検出するためのステロイド受容体アッセイ | |
Terstappen et al. | Flowcytometry‐Principles and Feasibility in Transfusion Medicine. Enumeration of Epithelial Derived Tumor Cells in Peripheral Blood | |
WO2006020936A2 (en) | A method for assessing disease states by profile analysis of isolated circulating endothelial cells | |
JP4590109B2 (ja) | 細胞の単一パラメータ及び複数パラメーター表現型解析のための生成物と方法 | |
JP2018021934A5 (ja) | ||
AU2018243850B2 (en) | Methods of using giant cell nucleic acid characterization in cancer screening, diagnostics, treatment and recurrence | |
US11994516B2 (en) | Composition, method and kit for pathology |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20171026 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180116 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20180809 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180911 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20181211 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190124 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190618 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190917 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20191105 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200205 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200421 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200520 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6707505 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |