WO2015061844A1 - Dosage pour stratifier des patients atteints du cancer - Google Patents

Dosage pour stratifier des patients atteints du cancer Download PDF

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Publication number
WO2015061844A1
WO2015061844A1 PCT/AU2014/050309 AU2014050309W WO2015061844A1 WO 2015061844 A1 WO2015061844 A1 WO 2015061844A1 AU 2014050309 W AU2014050309 W AU 2014050309W WO 2015061844 A1 WO2015061844 A1 WO 2015061844A1
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WO
WIPO (PCT)
Prior art keywords
assay
immunoglobulins
antigens
cll
solid support
Prior art date
Application number
PCT/AU2014/050309
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English (en)
Inventor
Richard Ian Christopherson
Pauline HUANG
Stephen Mulligan
Original Assignee
The University Of Sydney
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
Priority claimed from AU2013904183A external-priority patent/AU2013904183A0/en
Application filed by The University Of Sydney filed Critical The University Of Sydney
Publication of WO2015061844A1 publication Critical patent/WO2015061844A1/fr

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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
    • G01N33/57426—Specifically defined cancers leukemia
    • 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
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047—Cells of the immune system
    • G01N33/5052—Cells of the immune system involving B-cells
    • 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
    • G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/56—Staging of a disease; Further complications associated with the disease

Definitions

  • CLL chronic lymphocytic leukaemia
  • lymphoid organs such as lymph nodes and spleen
  • restin cells in peripheral blood resistant to apoptosis.
  • Heterogeneity with variable clinical courses is a hallmark of CLL (Shanafelt et al (2004) Blood 70J:1201-12.1.0).
  • Some patients live with stable disease for many years without intervention, while 20-30% follow an aggressive course, sometimes with rapid progression requiring treatment (Kay et aL (2002) Blood 100:1 110-11.11 ).
  • CLL is characterized by a unique immunophenotype of CD5 + .
  • CD 19* CD23 + with CD20 (dim/weak), CD22 (dim/weak), CD79b (dim/weak) and FMC7 (negative), surface immunoglobulin (sig, weak), often IgM with or without IgD (Matutes et al (2010) Best Pracl Res Clin Haematol 23:3-20).
  • B-cell expression of CD5 and CD23 is essentially diagnostic of CLL.
  • the DotScan (Trademark) CD antibody mieroarray overcomes this limitation for surface antigen profiling, providin very extensive immunophenotypes of any type of human ceil (Belov et al (2001) Cancer Res 67:4483-4489).
  • the surface profiles provide very extensive phenotypes that can be used as signatures for cancer subtypes (Belov et al (2006) Br J Haematol 735:184- 197).
  • the present specification enables an assay to stratify chronic lymphocytic leukemia (CLL) in a patient on the basis of whether it is a stable (S) or slow-progressive (SP) form of the disease, or whether it is a. progressive (P) form of the disease.
  • CLL chronic lymphocytic leukemia
  • S stable
  • SP slow-progressive
  • P progressive
  • Early knowledge of the form of CLL enables selection of appropriate therapeutic intervention based on the likely aggressiveness or otherwise of the disease. For example, P forms of CLL may require immediate chemotherapy whereas S/P forms of the disease may simply require regular observation.
  • the B-cells are contacted with the immunoglobulin array for a time and under conditions sufficient for B-cells to be captured based on the level of expression of particulai- CD antigens to which the immunoglobulins at each discrete site bind.
  • the CD antigens are selected to discriminate and differentiate between P and S/SP forms of CLL, Hence, the assay discriminates -cells from CLL patients on the signature of expression of. CD antigens wherein the relative abundance of bindin of B-cells to the discrete immunoglobulin sites of a microarray determines if the CLL is of a P form or an. S/SP form.
  • the present specification further enables an assay device comprising a carrier stage adapted to receive the solid support comprising the array of immunoglobulins and a scanner comprising a light source for illuminating the array of immunoglobulins on the solid support,
  • a drive means moves the carrier stage such that successive portions of the solid support are illuminated.
  • a digital camer system is disposed so that it captures successive portions of light ray which emerge from the solid support at an angle offset relative to the light rays from the light source. The resulting images are then reconstructed into an image of the array of immunoglobulins and cells bound thereto,
  • the color bar above the heat map represents the subtype of CLL as determined by established pathology criteria (Table 1); the color key for subtypes is on the left; red is progressive (P) CLL.
  • the color bars beneath th heat map are the results from fluorescence in situ hybridization (FISH) for the corresponding patient; not all CLL samples were subjected to FISH.
  • an assay and assay device useful in the stratification of chronic lymphocytic leukemia (CLL) int progressive (P) and stable (S)/slo -progressive (SP) [S/SP] forms.
  • CLL chronic lymphocytic leukemia
  • SP stable
  • A. single assa device is provided which comprises a solid support with an array of immunoglobulin molecules immobilized to discrete sites or regions of the solid support wherein the immunoglobulins in each discrete region are homogeneou with respect to binding specificity to a single CD antigen on a B-cel.1.
  • the immunoglobulins may bind to different epitopes on the one CD antigen.
  • B-cells will bind to the discrete region on the solid support, It is the relative abundance of B-eell binding which gives a signature- indicative of a P or S/SP form of CLL.
  • the CD antigens are selected on the basis of a clinically significant correlation between CD expression and one or other of P or S/S forms of CLL.
  • the B-cells are derived from a biologieal sample selected from whole blood, urine, lymph fluid, purulent discharge and a fraction of an of the above.
  • an assay to stratify a patient wit CLL int a P form or an S/SP form of CLL comprising contacting B -cells from the patient with an arra of immunoglobulins immobilized to discrete regions on a solid support wherein the immunoglobulins in each discrete region are homogeneous with respect to their specificity to a CD antigen on a B-cell or a control wherein the array of immunoglobulins is specific for at least 18 CD antigens selected to enable a differential abundance of binding to the CD antigens which distinguishes between a P tbrm and an.
  • an assay to stratify a patient with CLL into a P form or an S/SP form of CLL comprising contacting B-cells from the patient with an array of immunoglobulins immobilized to discrete regions on a solid support wherein the immunoglobulins in each discrete region are homogeneous with respect to their specificity to a CD antigen on a B-cell or a control wherein the array of immunoglobulins is specific for at least 22.
  • At least 27 CD antigens are chosen.
  • CD .1.8 CD19, CD20 (2 epitopes), CD21, CD22, CD23, CD24, CD25, CD38, CD4Q, CD43, CD45, CD45RA, CD52.
  • CDl 6 and CD270 wherein the differential abundance of binding to the CD antigens distinguishes between a P and an S/SP fonn of CLL, wherein a P patient exhibits greater binding to the at least 1.8 CD of the antigens compared t an S/SP patient.
  • At least 18 means 18, 1.9, 20, 21, 22, 23, 24, 25, 26 or 27. Any number of CD antigens may be substituted or added to the array of 18 to 27 discrete immunoglobulin regions t which a CD antigen binds, in an embodiment, the CD antigens comprise or are selected from the list of 27 CD antigens.
  • At least 18, 19, 20, 21, 22, 23, 24, 25, 26 or 27 CD antigens are selected.
  • One or more other CD antigens may be substantially for any o the 27 or added to the 27 CD antigens.
  • This aspect includes at least one reflector positioned to direct diffracted or otherwise deflected light rays emerging from the solid support at the offset angle towards an imaging lens of the camera system.
  • the digital optical camer system includes, in an embodiment, a line scan camera capable of sensing a linear image.
  • the digital optical camera system is disposed such that, in use, light rays emitted from fluorescent markers at the discrete immunoglobulin regions are captured.
  • Binet stage A o B may have mild splenomegaly, hepatomegal , ly mphadenopamy
  • CD antigens Differentially abundant CD antigens (27) between the three clinical subtypes of CLL; stable (S), slow-progressive (SP) and progressive (P). The results are shown in Table 3, The mean values represent levels of cells binding on DotSean (Trademark) antibody dots after background subtraction and normalisation. Mean P denotes the mean value of cell binding intensity on an antibody dot in the Progressive group. CD antigens are arranged in order of increasing mean intensity for the progressive sub-group The "IM" of CD20 IM distinguishes this Imnmiiotech antibody (clone B9E9(HRC20)) from the Beckman Coulter antibody 20 (clone H299(B 1)).

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Chemical & Material Sciences (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Pathology (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Oncology (AREA)
  • Hospice & Palliative Care (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Toxicology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

La présente invention porte sur des dosages pour stratifier une leucémie lymphoïde chronique (CLL) à lymphocytes B progressive à partir de formes stables ou progressives stables. Un microréseau d'anticorps est proposé, lequel est spécifique à au moins 18 des 27 antigènes CD suivants abondants différemment dans la CLL progressive : CD11a, CD11b, CD11c, CD18, CD19, CD20, (deux épitopes), CD21, CD22, CD23, CD24, CD25, CD38, CD40,CD43, CD45, CD45RA, CD52, CD69, CD81, CD84, CD98, CD102, CD148, CD180, CD196 et CD270.
PCT/AU2014/050309 2013-10-30 2014-10-27 Dosage pour stratifier des patients atteints du cancer WO2015061844A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AU2013904183A AU2013904183A0 (en) 2013-10-30 Assay to stratify cancer patients
AU2013904183 2013-10-30

Publications (1)

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WO2015061844A1 true WO2015061844A1 (fr) 2015-05-07

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Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110719959A (zh) * 2017-06-05 2020-01-21 贝克顿迪金森公司 针对单细胞的样品索引
CN111665235A (zh) * 2019-03-08 2020-09-15 上海索昕生物科技有限公司 一种化学发光微阵列芯片及其应用
US10941396B2 (en) 2012-02-27 2021-03-09 Becton, Dickinson And Company Compositions and kits for molecular counting
US10954570B2 (en) 2013-08-28 2021-03-23 Becton, Dickinson And Company Massively parallel single cell analysis
US11220685B2 (en) 2016-05-31 2022-01-11 Becton, Dickinson And Company Molecular indexing of internal sequences
USRE48913E1 (en) 2015-02-27 2022-02-01 Becton, Dickinson And Company Spatially addressable molecular barcoding
US11319583B2 (en) 2017-02-01 2022-05-03 Becton, Dickinson And Company Selective amplification using blocking oligonucleotides
US11332776B2 (en) 2015-09-11 2022-05-17 Becton, Dickinson And Company Methods and compositions for library normalization
US11365409B2 (en) 2018-05-03 2022-06-21 Becton, Dickinson And Company Molecular barcoding on opposite transcript ends
US11460468B2 (en) 2016-09-26 2022-10-04 Becton, Dickinson And Company Measurement of protein expression using reagents with barcoded oligonucleotide sequences
US11492660B2 (en) 2018-12-13 2022-11-08 Becton, Dickinson And Company Selective extension in single cell whole transcriptome analysis
US11525157B2 (en) 2016-05-31 2022-12-13 Becton, Dickinson And Company Error correction in amplification of samples
US11535882B2 (en) 2015-03-30 2022-12-27 Becton, Dickinson And Company Methods and compositions for combinatorial barcoding
US11639517B2 (en) 2018-10-01 2023-05-02 Becton, Dickinson And Company Determining 5′ transcript sequences
US11649497B2 (en) 2020-01-13 2023-05-16 Becton, Dickinson And Company Methods and compositions for quantitation of proteins and RNA
US11661631B2 (en) 2019-01-23 2023-05-30 Becton, Dickinson And Company Oligonucleotides associated with antibodies
US11661625B2 (en) 2020-05-14 2023-05-30 Becton, Dickinson And Company Primers for immune repertoire profiling
US11739443B2 (en) 2020-11-20 2023-08-29 Becton, Dickinson And Company Profiling of highly expressed and lowly expressed proteins
US11773441B2 (en) 2018-05-03 2023-10-03 Becton, Dickinson And Company High throughput multiomics sample analysis
US11773436B2 (en) 2019-11-08 2023-10-03 Becton, Dickinson And Company Using random priming to obtain full-length V(D)J information for immune repertoire sequencing
US11845986B2 (en) 2016-05-25 2023-12-19 Becton, Dickinson And Company Normalization of nucleic acid libraries
US11932901B2 (en) 2020-07-13 2024-03-19 Becton, Dickinson And Company Target enrichment using nucleic acid probes for scRNAseq
US11932849B2 (en) 2018-11-08 2024-03-19 Becton, Dickinson And Company Whole transcriptome analysis of single cells using random priming
US11939622B2 (en) 2019-07-22 2024-03-26 Becton, Dickinson And Company Single cell chromatin immunoprecipitation sequencing assay
US11970737B2 (en) 2009-12-15 2024-04-30 Becton, Dickinson And Company Digital counting of individual molecules by stochastic attachment of diverse labels
US12071617B2 (en) 2019-02-14 2024-08-27 Becton, Dickinson And Company Hybrid targeted and whole transcriptome amplification

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US12060607B2 (en) 2009-12-15 2024-08-13 Becton, Dickinson And Company Digital counting of individual molecules by stochastic attachment of diverse labels
US11993814B2 (en) 2009-12-15 2024-05-28 Becton, Dickinson And Company Digital counting of individual molecules by stochastic attachment of diverse labels
US11970737B2 (en) 2009-12-15 2024-04-30 Becton, Dickinson And Company Digital counting of individual molecules by stochastic attachment of diverse labels
US10941396B2 (en) 2012-02-27 2021-03-09 Becton, Dickinson And Company Compositions and kits for molecular counting
US11634708B2 (en) 2012-02-27 2023-04-25 Becton, Dickinson And Company Compositions and kits for molecular counting
US10954570B2 (en) 2013-08-28 2021-03-23 Becton, Dickinson And Company Massively parallel single cell analysis
US11702706B2 (en) 2013-08-28 2023-07-18 Becton, Dickinson And Company Massively parallel single cell analysis
US11618929B2 (en) 2013-08-28 2023-04-04 Becton, Dickinson And Company Massively parallel single cell analysis
USRE48913E1 (en) 2015-02-27 2022-02-01 Becton, Dickinson And Company Spatially addressable molecular barcoding
US11535882B2 (en) 2015-03-30 2022-12-27 Becton, Dickinson And Company Methods and compositions for combinatorial barcoding
US11332776B2 (en) 2015-09-11 2022-05-17 Becton, Dickinson And Company Methods and compositions for library normalization
US11845986B2 (en) 2016-05-25 2023-12-19 Becton, Dickinson And Company Normalization of nucleic acid libraries
US11525157B2 (en) 2016-05-31 2022-12-13 Becton, Dickinson And Company Error correction in amplification of samples
US11220685B2 (en) 2016-05-31 2022-01-11 Becton, Dickinson And Company Molecular indexing of internal sequences
US11460468B2 (en) 2016-09-26 2022-10-04 Becton, Dickinson And Company Measurement of protein expression using reagents with barcoded oligonucleotide sequences
US11467157B2 (en) 2016-09-26 2022-10-11 Becton, Dickinson And Company Measurement of protein expression using reagents with barcoded oligonucleotide sequences
US11782059B2 (en) 2016-09-26 2023-10-10 Becton, Dickinson And Company Measurement of protein expression using reagents with barcoded oligonucleotide sequences
US11319583B2 (en) 2017-02-01 2022-05-03 Becton, Dickinson And Company Selective amplification using blocking oligonucleotides
US12084712B2 (en) 2017-06-05 2024-09-10 Becton, Dickinson And Company Sample indexing for single cells
CN110719959A (zh) * 2017-06-05 2020-01-21 贝克顿迪金森公司 针对单细胞的样品索引
CN110719959B (zh) * 2017-06-05 2021-08-06 贝克顿迪金森公司 针对单细胞的样品索引
US11773441B2 (en) 2018-05-03 2023-10-03 Becton, Dickinson And Company High throughput multiomics sample analysis
US11365409B2 (en) 2018-05-03 2022-06-21 Becton, Dickinson And Company Molecular barcoding on opposite transcript ends
US11639517B2 (en) 2018-10-01 2023-05-02 Becton, Dickinson And Company Determining 5′ transcript sequences
US11932849B2 (en) 2018-11-08 2024-03-19 Becton, Dickinson And Company Whole transcriptome analysis of single cells using random priming
US11492660B2 (en) 2018-12-13 2022-11-08 Becton, Dickinson And Company Selective extension in single cell whole transcriptome analysis
US11661631B2 (en) 2019-01-23 2023-05-30 Becton, Dickinson And Company Oligonucleotides associated with antibodies
US12071617B2 (en) 2019-02-14 2024-08-27 Becton, Dickinson And Company Hybrid targeted and whole transcriptome amplification
CN111665235A (zh) * 2019-03-08 2020-09-15 上海索昕生物科技有限公司 一种化学发光微阵列芯片及其应用
US11939622B2 (en) 2019-07-22 2024-03-26 Becton, Dickinson And Company Single cell chromatin immunoprecipitation sequencing assay
US11773436B2 (en) 2019-11-08 2023-10-03 Becton, Dickinson And Company Using random priming to obtain full-length V(D)J information for immune repertoire sequencing
US11649497B2 (en) 2020-01-13 2023-05-16 Becton, Dickinson And Company Methods and compositions for quantitation of proteins and RNA
US11661625B2 (en) 2020-05-14 2023-05-30 Becton, Dickinson And Company Primers for immune repertoire profiling
US11932901B2 (en) 2020-07-13 2024-03-19 Becton, Dickinson And Company Target enrichment using nucleic acid probes for scRNAseq
US11739443B2 (en) 2020-11-20 2023-08-29 Becton, Dickinson And Company Profiling of highly expressed and lowly expressed proteins

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