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US 2024/0201191 A1Published application
Citrullinated proteins as biomarkers and therapy targets for cancer
OwnerSamir HANASH, Hiroyuki KATAYAMAinventors
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Abstract
Provided herein are methods of detecting cancer, diagnosing a subject with cancer, treating a subject with cancer, and reducing the risk of or preventing cancer in a subject. The methods are based in part on the discovery of dysregulated protein citrullination by protein arginine deaminase enzymes in cancer. Also provided are citrullinated peptides and kits that are expressed at a higher level in cancer cells than in corresponding normal cells. Kits and systems relating to these methods are also provided.
Claims52
A method, comprising:
- providing a plasma sample from a patient suffering from a cancer or suspected of suffering from the cancer;
- incubating the plasma sample with at least one citrullinated protein selected from the group consisting of the proteins encoded by genes listed in Table 1, the proteins encoded by genes listed in Table 2, and the proteins encoded by genes listed in Table 10, under conditions sufficient for any autoantibodies against the citrullinated protein(s) that may be present in the plasma sample, to bind to the citrullinated protein(s);
- incubating the citrullinated protein(s) and any bound autoantibodies against it/them with a detectable label, under conditions in which the detectable label will bind to the bound autoantibodies and will substantially not bind to other molecules;
- detecting the detectable label bound to the bound autoantibodies;
- classifying the patient as suffering from the cancer in response to the detected amount of the detectable label bound to the bound autoantibodies being equal to or greater than a threshold;
- and
- classifying the patient as not suffering from the cancer in response to the detected amount of the detectable label bound to the bound autoantibodies being less than the threshold.
4 more elements
A kit, comprising:
- a substrate;
- at least one citrullinated protein selected from the group consisting of the proteins encoded by genes listed in Table 1, the proteins encoded by genes listed in Table 2, and the proteins encoded by genes listed in Table 10;
- and
- instructions for performing a method, comprising instructions to:
- provide a plasma sample from a patient suffering from a cancer or suspected of suffering from the cancer;
- incubate the plasma sample with the citrullinated protein(s) under conditions sufficient for any autoantibodies against the citrullinated protein(s) that may be present in the plasma sample, to bind to the citrullinated protein(s);
- incubate the citrullinated protein(s) and any bound autoantibodies against it/them with a detectable label, under conditions wherein the detectable label will bind to the bound autoantibodies and will substantially not bind to other molecules;
- detect the label bound to the bound autoantibodies;
- classify the patient as suffering from the cancer, in response to the detected amount of the label bound to the bound autoantibodies being equal to or greater than a threshold;
- and
- classify the patient as not suffering from the cancer, in response to the detected amount of the label bound to the bound autoantibodies being less than the threshold.
8 more elements
A method, comprising:
- providing a tissue sample from a patient suffering from a cancer or suspected of suffering from the cancer;
- assaying the tissue sample for at least one citrullinated protein selected from the group consisting of the proteins encoded by genes listed in Table 1, the proteins encoded by genes listed in Table 2, and the proteins encoded by genes listed in Table 10;
- classifying the patient as suffering from the cancer in response to the tissue sample containing an amount of the citrullinated protein(s) equal to or greater than a threshold;
- and
- classifying the patient as not suffering from the cancer in response to the tissue sample containing an amount of the citrullinated protein(s) less than the threshold.
2 more elements
A kit, comprising:
- a cell lysis agent;
- and
- instructions for performing a method, comprising instructions to:
- provide a tissue sample from a patient suffering from a cancer or suspected of suffering from the cancer;
- lyse cells of the tissue sample by exposing the tissue sample to the cell lysis agent;
- assay the tissue sample for at least one citrullinated protein selected from the group consisting of the proteins encoded by genes listed in Table 1, the proteins encoded by genes listed in Table 2, and the proteins encoded by genes listed in Table 10;
- classify the patient as suffering from the cancer, in response to the tissue sample containing an amount of the citrullinated protein(s) equal to or greater than a threshold;
- and
- classify the patient as not suffering from the cancer, in response to the tissue sample containing an amount of the citrullinated protein(s) less than the threshold.
6 more elements
A method, comprising:
- providing a tumor sample from a patient suffering from a cancer;
- assaying the tumor sample for at least one citrullinated amino acid sequence selected from the group consisting of sequences and corresponding modifications listed in Table 2, Table 9, and/or Table 10, and sequences having at least 70% identity to the sequences listed in Table 2, Table 9, and/or Table 10 and comprising at least one arginine residue;
- and
- presenting to the immune system of the patient at least one peptide, wherein each peptide comprises at least one of the citrullinated amino acid sequences, in response to the tumor sample containing an amount of the citrullinated amino acid sequence(s) equal to or greater than a threshold.
1 more element
A kit, comprising:
- at least one peptide, wherein each peptide comprises at least one citrullinated amino acid sequence selected from the group consisting of sequences and corresponding modifications listed in Table 2, Table 9, and/or Table 10, and sequences having at least 70% identity to the sequences listed in Table 2, Table 9, and/or Table 10 and comprising at least one arginine residue;
- and
- instructions for performing a method, comprising instructions to:
- provide a tumor sample from a patient suffering from a cancer;
- assay the tumor sample for the citrullinated amino acid sequence(s) contained in each of the peptide(s);
- and
- present to the immune system of the patient one or more of the peptides, in response to the tumor sample containing an amount equal to or greater than a threshold of the citrullinated amino acid sequence contained in the peptide(s).
4 more elements
A method, comprising:
- providing a tumor sample from a patient suffering from a cancer;
- assaying the tumor sample for a citrullinated protein encoded by a gene selected from the group consisting of genes listed in Table 1 as having a plasma membrane location;
- and
- administering to the patient an anti-cancer agent targeting the citrullinated protein, in response to the tumor sample containing an amount of the citrullinated protein equal to or greater than a threshold.
1 more element
A kit, comprising:
- an anti-cancer agent targeting a citrullinated protein encoded by a gene selected from the group consisting of genes listed in Table 1 as having a plasma membrane location;
- and
- instructions for performing a method, comprising instructions to:
- provide a tumor sample from a patient suffering from a cancer;
- assay the tumor sample for the citrullinated protein;
- and
- administer to the patient an anti-cancer agent targeting the citrullinated protein, in response to the tumor sample containing an amount of the citrullinated protein equal to or greater than a threshold.
4 more elements
An isolated peptide comprising at least 70% sequence identity to a peptide selected from the group consisting of peptides listed in Table 2, Table 9, and Table 10.
Dependencies are inferred from the claim text.