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US 2020/0025766 A1Published application
Methods for the detection and treatment of lung cancer
AssigneeBoard of Regents, The University of Texas System
InventorsSamir HANASH, Ayumu TAGUCHI, Ziding FENG
Life of this patent
Estimating the term…
Abstract
Provided are methods and related kits for detection of early stage lung cancer, and determination of risk of harboring lung cancer.
Claims228
A method of determining the risk of a subject for harboring lung cancer, comprising obtaining a biological sample from the subject;
- measuring the level of CEA in the biological sample;
- measuring the level of CA125 in the biological sample;
- measuring the level of CYFRA21-1 in the biological sample;
- measuring the level of Pro-SFTPB in the biological sample;
- wherein the amount of CEA, CA125, CYFRA21-1, and Pro-SFTPB classifies the subject as being at risk of harboring lung cancer or not at risk of harboring lung cancer.
2 more elements
A method of determining the risk of a subject for harboring lung cancer, comprising obtaining a biological sample from the subject;
- contacting the sample with a first reporter molecule that binds CEA;
- contacting the sample with a second reporter molecule that binds CA125;
- contacting the sample with a third reporter molecule that binds CYFRA21-1;
- contacting the sample with a fourth reporter molecule that binds Pro-SFTPB;
- wherein the amount of the first reporter molecule, the second reporter molecule, the third reporter molecule, and the fourth reporter molecule classifies the subject as being at risk of harboring lung cancer or not at risk of harboring lung cancer.
2 more elements
A method of determining the risk of a subject for harboring lung cancer, comprising obtaining a biological sample from the subject;
- providing a surface that binds CEA, CA125, CYFRA21-1, and Pro-SFTPB;
- incubating the surface with the biological sample;
- contacting the surface with a first reporter molecule that binds CEA;
- contacting the surface with a second reporter molecule that binds CA125;
- contacting the surface with a third reporter molecule that binds CYFRA21-1;
- contacting the surface with a fourth reporter molecule that binds Pro-SFTPB;
- measuring the amount of the first reporter molecule that is associated with the surface;
- measuring the amount of the second reporter molecule that is associated with the surface;
- measuring the amount of the third reporter molecule that is associated with the surface;
- measuring the amount of the fourth reporter molecule that is associated with the surface;
- wherein the amount of the first reporter molecule, the second reporter molecule, the third reporter molecule, and the fourth reporter molecule classifies the subject as being at risk of harboring lung cancer or not at risk of harboring lung cancer.
8 more elements
A method of determining the risk of a subject for harboring lung cancer, comprising obtaining a biological sample from the subject;
- providing a first surface with means for binding CEA;
- providing a second surface with means for binding CA125;
- providing a third surface with means for binding CYFRA21-1;
- providing a fourth surface with means for binding Pro-SFTPB;
- incubating the first surface with the biological sample;
- incubating the second surface with the biological sample;
- incubating the third surface with the biological sample;
- incubating the fourth surface with the biological sample;
- contacting the first surface with a first reporter molecule that binds CEA;
- contacting the second surface with a second reporter molecule that binds CA125;
- contacting the third surface with a third reporter molecule that binds CYFRA21-1;
- contacting the fourth surface with a third reporter molecule that binds pro-SFTPB;
- measuring the amount of the first reporter molecule associated with the first surface;
- measuring the amount of the second reporter molecule associated with the second surface;
- measuring the amount of the third reporter molecule associated with the third surface;
- measuring the amount of the third reporter molecule associated with the fourth surface;
- wherein the amount of the first reporter molecule, the second reporter molecule, the third reporter molecule, and the fourth reporter molecule classifies the subject as being at risk of harboring lung cancer or not at risk of harboring lung cancer.
14 more elements
A method of determining the risk of a subject for harboring lung cancer, comprising obtaining a biological sample from the subject;
- providing a surface with means for binding CEA, CA125, CYFRA21-1, and Pro-SFTPB;
- incubating the surface with the biological sample;
- contacting the surface with a first relay molecule that binds CEA;
- contacting the surface with a second relay molecule that binds CA125;
- contacting the surface with a third relay molecule that binds CYFRA21-1;
- contacting the surface with a fourth relay molecule that binds Pro-SFTPB;
- contacting the surface with a first reporter molecule that binds to the first relay molecule;
- contacting the surface with a second reporter molecule that binds to the second relay molecule;
- contacting the surface with a third reporter molecule that binds to the third relay molecule;
- contacting the surface with a fourth reporter molecule that binds to the fourth relay molecule;
- measuring the amount of the first reporter molecule associated with the first relay molecule and CEA;
- measuring the amount of the second reporter molecule associated with the second relay molecule and CA125;
- measuring the amount of the third reporter molecule associated with the third relay molecule and CYFRA21-1;
- measuring the amount of the fourth reporter molecule associated with the fourth relay molecule and Pro-SFTPB;
- wherein the amount of the first reporter molecule, the second reporter molecule, the third reporter molecule, and the fourth reporter molecule classifies the subject as being at risk of harboring lung cancer or not at risk of harboring lung cancer.
12 more elements
A method of determining the risk of a subject for harboring lung cancer, comprising obtaining a biological sample from the subject;
- providing a first surface with means for binding CEA;
- providing a second surface with means for binding CA125;
- providing a third surface with means for binding CYFRA21-1;
- providing a fourth surface with means for binding Pro-SFTPB;
- incubating the first surface with the biological sample;
- incubating the second surface with the biological sample;
- incubating the third surface with the biological sample;
- incubating the fourth surface with the biological sample;
- contacting the first surface with a first relay molecule that binds CEA;
- contacting the second surface with a second relay molecule that binds CA125;
- contacting the third surface with a third relay molecule that binds CYFRA21-1;
- contacting the fourth surface with a fourth relay molecule that binds Pro-SFTPB;
- contacting the first surface with a first reporter molecule that binds to the first relay molecule;
- contacting the second surface with a second reporter molecule that binds to the second relay molecule;
- contacting the third surface with a third reporter molecule that binds to the third relay molecule;
- contacting the fourth surface with a fourth reporter molecule that binds to the fourth relay molecule;
- measuring the amount of the first reporter molecule that is associated with the first relay molecule and CEA;
- measuring the amount of the second reporter molecule that is associated with the second relay molecule and CA125;
- measuring the amount of the third reporter molecule that is associated with the third relay molecule and CYFRA21-1;
- measuring the amount of the fourth reporter molecule that is associated with the fourth relay molecule and Pro-SFTPB;
- wherein the amount of the first reporter molecule, the second reporter molecule, the third reporter molecule, and the fourth reporter molecule classifies the subject as being at risk of harboring lung cancer or not at risk of harboring lung cancer.
18 more elements
A method of determining the risk of a subject for harboring lung cancer, comprising
- obtaining a biological sample from the subject;
- measuring the level of CEA in the biological sample by contacting the biological sample with a CEA antibody and observing binding between CEA and the antibody;
- measuring the level of CA125 in the biological sample by contacting the biological sample with a CA125 antibody and observing binding between CA125 and the antibody;
- measuring the level of CYFRA21-1 in the biological sample by contacting the biological sample with a CYFRA21-1 antibody and observing binding between CYFRA21-1 and the antibody;
- measuring the level of pro-SFTPB in the biological sample by contacting the biological sample with a pro-SFTPB antibody and observing binding between pro-SFTPB and the antibody;
- assigning the condition of the subject as either at risk of harboring lung cancer or not at risk of harboring lung cancer, as determined by the measurements of CEA, CA125, CYFRA21-1, and pro-SFTPB levels.
3 more elements
A method of determining the risk of a subject for harboring lung cancer, comprising
- obtaining a biological sample from the subject;
- measuring the level of CEA in the biological sample;
- measuring the level of CA125 in the biological sample;
- measuring the level of CYFRA21-1 in the biological sample;
- measuring the level of pro-SFTPB in the biological sample;
- determining the level of CEA relative to a first standard value, wherein the ratio is predictive of presence of lung cancer;
- determining the level of CA125 relative to a second standard value, wherein the ratio is predictive of presence of lung cancer;
- determining the level of CYFRA21-1 relative to a third standard value, wherein the ratio is predictive of presence of lung cancer;
- and
- determining the level of pro-SFTPB relative to a fourth standard value, wherein the ratio is predictive of presence of lung cancer;
- and
- assigning the condition of the subject as either at risk of harboring lung cancer or not at risk of harboring lung cancer, as determined by statistical analysis of the ratios of CEA, CA125, CYFRA21-1, and pro-SFTPB levels.
9 more elements
A method of predicting the risk of a subject for harboring lung, comprising
- obtaining a biological sample from the subject;
- measuring the levels of the CEA, CA125, CYFRA21-1, and pro-SFTPB biomarkers in the biological sample;
- and
- calculating a predictive factor as determined by statistical analysis of the CEA, CA125, CYFRA21-1, and pro-SFTPB levels.
1 more element
A method of determining the risk of a subject for harboring lung cancer, comprising obtaining a biological sample from the subject;
- measuring the levels of CEA, CA125, CYFRA21-1, and pro-SFTPB biomarkers in the biological sample;
- assigning the condition of the subject as either at risk of harboring lung cancer or not at risk of harboring lung cancer, as determined by statistical analysis of the levels of CEA, CA125, CYFRA21-1, and pro-SFTPB in the biological sample.
A method for determining the risk of a subject for harboring lung cancer using a biological sample obtained from a subject suspected of having lung cancer, comprising assaying for the level of CEA present in the biological sample using at least one antibody or antibody fraction specific for CEA;
- and
- assaying for the level of CA125 present in the biological sample using at least one antibody or antibody fraction specific for CA125;
- and
- assaying for the level of CYFRA21-1 present in the biological sample using at least one antibody or antibody fraction specific for CYFRA21-1;
- and
- assaying for the level of pro-SFTPB present in the biological sample using at least one antibody or antibody fraction specific for pro-SFTPB;
- and
- determining whether the levels of CEA, CA125, CYFRA21-1, and pro-SFTPB are indicative of the subject having lung cancer.
5 more elements
A method for determining the risk of a subject for harboring lung cancer comprising obtaining a biological sample sample from a subject;
- performing an immunoassay on the sample with an anti-CEA antibody or antigen-binding fragment thereof;
- performing an immunoassay on the sample with an anti-CA125 antibody or antigen-binding fragment thereof;
- performing an immunoassay on the sample with an anti-CYFRA21-1 antibody or antigen-binding fragment thereof;
- performing an immunoassay on the sample with an anti-pro-SFTPB antibody or antigen-binding fragment thereof;
- wherein binding of the antibodies is indicative of lung cancer in the subject and the immunoassay can detect early stage lung cancer.
2 more elements
A method for determining the risk of a subject for harboring lung cancer comprising
- obtaining a biological sample sample from the subject;
- performing an immunoassay with an anti-CEA antibody or antigen-binding fragment thereof;
- performing an immunoassay with an anti-CA125 antibody or antigen-binding fragment thereof;
- performing an immunoassay with an anti-CYFRA21-1 antibody or antigen-binding fragment thereof;
- performing an immunoassay with an anti-pro-SFTPB antibody or antigen-binding fragment thereof;
- determining whether the levels of CEA, CA125, CYFRA21-1, and pro-SFTPB are indicative of the subject having lung cancer.
3 more elements
A method of determining the risk of a subject for harboring lung cancer, comprising
- obtaining a biological sample from the patient;
- measuring the level of diacetylspermine (DAS) in the biological sample;
- wherein the amount of diacetylspermine (DAS) classifies the subject as being at risk of harboring lung cancer or not at risk of harboring lung cancer.
A method of determining the risk of a subject for harboring lung cancer, comprising a plasma-derived biomarker panel and a protein marker panel:
- wherein the plasma-derived biomarker panel comprises diacetylspermine (DAS);
- wherein the protein biomarker panel comprises CEA, CA125, CYFRA21-1, and pro-SFTPB;
- wherein the method comprises:
- obtaining a biological sample from the subject;
- measuring the levels of the plasma-derived biomarkers and the protein biomarkers in the biological sample;
- wherein the amount of the plasma-derived biomarkers and the protein biomarkers classifies the subject as being at risk of harboring lung cancer or not at risk of harboring lung cancer.
3 more elements
A method of determining the risk of a subject for harboring lung cancer, comprising determining the levels of one or more protein biomarkers and one or more metabolite markers, said method comprising:
- obtaining a biological sample from the subject;
- contacting the sample with a first reporter molecule that binds CEA antigen;
- contacting the sample with a second reporter molecule that binds CA125 antigen;
- contacting the sample with a third reporter molecule that binds CYFRA21-1 antigen;
- and
- contacting the sample with a fourth reporter molecule that binds pro-SFTPB antigen;
- and
- determining the levels of the one or more biomarkers, wherein the one or more biomarkers is selected from the group consisting of diacetylspermine (DAS);
- wherein the amount of the first reporter molecule, the second reporter molecule, the third reporter molecule, the fourth reporter molecule, and the one or more biomarkers classifies the subject as being at risk of harboring lunc cancer or not at risk of harboring lung cancer.
6 more elements
A method of determining the risk of a subject for harboring lung cancer, comprising
- obtaining a biological sample from the subject;
- measuring the levels of CEA, CA125, CYFRA21-1, and pro-SFTPB antigens in the biological sample;
- and
- measuring the levels of one or more metabolite markers selected from the group consisting of diacetylspermine (DAS) in the biological sample;
- assigning the condition of the subject as either at risk of harboring lung cancer or not at risk of harboring lung cancer, as determined by statistical analysis of the levels of CEA antigen, CA125 antigen, CYFRA21-1 antigen, pro-SFTPB antigen, and diacetylspermine (DAS) in the biological sample.
2 more elements
A method of treatment or prevention of progression of lung cancer in a subject in whom the levels of CEA antigen, CA125 antigen, CYFRA21-1 antigen, and pro-SFTPB antigen classifies the subject as having or being at risk of harboring lung cancer comprising one or more of:
- i. administering a chemotherapeutic drug to the subject with lung cancer;
- ii. administering therapeutic radiation to the subject with lung cancer;
- and
- iii. surgery for partial or complete surgical removal of cancerous tissue in the subject with lung cancer.
1 more element
A method of treatment or prevention of progression of lung cancer in a subject in whom the levels of CEA antigen, CA125 antigen, CYFRA21-1 antigen, pro-SFTPB antigen, diacetylspermine (DAS) classifies the subject as having or being at risk of harboring lung cancer comprising one or more of:
- i) administering a chemotherapeutic drug to the subject with lung cancer;
- ii) administering therapeutic radiation to the subject with lung cancer;
- and
- iii) surgery for partial or complete surgical removal of cancerous tissue in the subject with lung cancer.
1 more element
A method for detecting and treating lung cancer, comprising:
- detecting CEA, CA125, CYFRA21-1, and pro-SFTPB, in a biological sample obtained from a human, via an immunoassay;
- quantifying the amounts CEA, CA125, CYFRA21-1, and pro-SFTPB in said collected sample;
- comparing the amounts of CEA, CA125, CYFRA21-1, and pro-SFTPB with a cutoff value to determine whether said human is at increased risk of having lung cancer or not;
- wherein if the levels are above the cutoff value said human has lung cancer, and administering a treatment for lung cancer to said human having lung cancer.
1 more element
A method of determining risk of a subject of harboring lung cancer, comprising:
- in a biological sample from a subject in need of analysis, measuring the concentration of CEA, CA125, CYFRA21-1, and Pro-SFTPB;
- and
- comparing the concentration of the biomarkers in the samples of the subject in need of analysis and the concentration in a normal or non-diseased subject,
- wherein the subject in need of analysis has or is at risk of harboring lung cancer, wherein the determination is based on a cutoff value at a sensitivity or specificity value as set forth in Table 10.
1 more element
A method of determining evidence of lung cancer in a biological sample, comprising measuring the concentration of a biomarker panel comprising CEA, CA125, CYFRA21-1, Pro-SFTPB, and diacetylspermine (DAS), and identifiable parts thereof in a biological sample from a subject, wherein a change in the concentration of each of the biomarkers based on a sensitivity or specificity for a cutoff set forth in Table 10 is characteristic of lung cancer.
The method of any of claims 159-179, wherein the concentrations of CEA, CA125, CYFRA21-1, Pro-SFTPB, and diacetylspermine (DAS) are measured.
A kit for determining the presence of indicators of lung cancer in a sample from the subject comprising:
- (a) antigen-binding reagents that bind to each of the protein biomarkers selected from the group consisting of CEA, CA125, CYFRA21-1, and pro-SFTPB, or an array comprising said antigen-binding reagents;
- and
- (b) instructions for performing a method for determining the presence of lung cancer in an individual.
A method comprising:
- a) obtaining a sample from a subject asymptomatic for lung cancer;
- b) measuring a panel of markers in the sample, wherein the markers comprise CEA, CA125, Cyfra 21-1, and diacetylspermine (DAS);
- c) determining a biomarker score for each marker;
- d) summing the biomarker scores for each marker to obtain a composite score for each subject, quantifying the increased risk for the presence of lung cancer for the subject as a risk score, wherein the composite score is matched to a risk category of a grouping of stratified subject populations, wherein each risk category comprises a multiplier indicating increased likelihood of having the lung cancer correlated to a range of composite scores as compared to use of a single threshold value, wherein the multiplier is determined from positive predictive scores of retrospective samples;
- and,
- e) administering a computerized tomography (CT) scan or other imagine modality to the subject with a quantified increased risk for the presence of lung cancer.
3 more elements
Dependencies are inferred from the claim text.