Biomarkers for the early detection of breast cancer
Inventors
Labaer, Joshua • Anderson, Karen Sue • Wallstrom, Garrick • Sibani, Sahar • Ramachandran, Niroshan
Assignees
Dana Farber Cancer Institute Inc • Harvard University • Arizona's Public Universities • Arizona State University ASU
Publication Number
US-11624747-B2
Publication Date
2023-04-11
Expiration Date
2031-08-15
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Abstract
The present invention provides reagents and methods for breast cancer detection.
Core Innovation
The present invention provides polypeptide probe sets, polynucleotide arrays, and methods for the detection of breast cancer. Specifically, the invention utilizes at least two different isolated polypeptides or their antigenic fragments selected from a defined group of tumor antigens, which are used to detect tumor antigen-specific autoantibodies in bodily fluid samples. The presence of these autoantibodies serves as a biomarker indicative of a likelihood of breast cancer in the tested subject.
The problem addressed by this invention is the need for biomarkers that can detect early stage breast cancer, monitor disease progression and recurrence, and predict responses to therapeutic interventions. Prior proteomics-based approaches have struggled with identifying small protein fragments in complex mixtures, protein instability, and variability among patient populations, making reliable detection challenging. Autoantibodies (AAb) to tumor antigens, while highly specific, tend to have poor sensitivity, but combining multiple antigens in parallel may increase the predictive value for breast cancer diagnostics.
By developing probe sets and arrays comprising selected polypeptides, as well as providing methods for detecting antibodies specific to these polypeptides, the invention enables accurate, simultaneous screening of multiple breast cancer biomarkers. The technology includes using customizable arrays (e.g., NAPPA protein microarrays) to present these antigens for detection of autoantibodies in patient serum or plasma, offering a platform for high-throughput immunodiagnostics targeting early detection of breast cancer.
Claims Coverage
The independent claims focus on a polypeptide probe set with specifically defined components and characteristics. There is one main inventive feature outlined in the independent claim.
Polypeptide probe set with specific breast cancer-related antigens and detectable tags
The inventive feature comprises a polypeptide probe set containing: - An isolated SF3A1 (SEQ ID NO: 2) polypeptide (or antigenic fragment thereof) - An isolated UBAP1 (SEQ ID NO: 47) polypeptide (or antigenic fragment thereof) - One or more additional isolated polypeptides selected from the group consisting of ATP6AP1 (SEQ ID NO: 13), PDCD6IP (SEQ ID NO: 21), DBT (SEQ ID NO: 25), CSNK1E (SEQ ID NO: 9), FRS3 (SEQ ID NO: 3), HOXD1 (SEQ ID NO: 7), C15orf48 (SEQ ID NO: 35), MYOZ2 (SEQ ID NO: 33), BAT4 (SEQ ID NO: 5), BMX (SEQ ID NO: 45), RAB5A (SEQ ID NO: 23), GPR157 (SEQ ID NO: 43), ZMYM6 (SEQ ID NO: 41), SLC33A1 (SEQ ID NO: 11), TRIM32 (SEQ ID NO: 37), ALG10 (SEQ ID NO: 27), TFCP2 (SEQ ID NO: 49), SERPINH1 (SEQ ID NO: 51), SELL (SEQ ID NO: 55), ZNF510 (SEQ ID NO: 53), or their antigenic fragments. The probe set is limited to no more than 100 different polypeptides. Each polypeptide in the set must have a detectable tag, with the requirement that the tag is not a naturally occurring part of the isolated polypeptide.
In summary, the independent claim secures a polypeptide probe set specifically composed of two required polypeptides (SF3A1 and UBAP1), at least one from a defined list, no more than 100 in total, each comprising a non-naturally occurring detectable tag.
Stated Advantages
The polypeptide probe sets enable the detection of tumor antigen-specific autoantibodies in bodily fluids from patients with breast cancer, including early-stage cases.
Autoantibodies to tumor antigens are stable, highly specific, easily purified from serum, and readily detected using well-validated secondary reagents.
Testing multiple antigens in parallel may increase the predictive value of tumor-specific antibodies for use as immunodiagnostics.
Protein microarrays allow for the simultaneous presentation and assessment of hundreds of tumor antigens, requiring only small amounts of serum per assay.
The methods can result in an accurate diagnosis in at least 70% of cases, with greater accuracy percentages possible.
Documented Applications
Detection of breast cancer, including early-stage breast cancer, by identifying autoantibodies to tumor antigens in bodily fluid samples from subjects at risk.
Monitoring disease progression and recurrence in breast cancer patients through detection of specific autoantibodies.
Providing diagnostic and prognostic information to attending physicians regarding the likelihood of breast cancer in tested subjects.
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