Plasma autoantibody biomarkers for basal like breast cancer
Inventors
Labaer, Joshua • Wang, Jie • Qui, Ji • Wallstrom, Garrick • Anderson, Karen • Park, Jin • Figueroa, Jonine
Assignees
US Department of Health and Human Services • Arizona State University Downtown Phoenix campus
Publication Number
US-11525831-B2
Publication Date
2022-12-13
Expiration Date
2035-12-09
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Abstract
Cancer patients make antibodies to tumor-derived proteins that are potential biomarkers for early detection. Twenty-eight antigens have been identified as potential biomarkers for the early detection of basal-like breast cancer (Tables 1, 2). Also, a 13-AAb classifier has been developed that differentiate patients with BLBC from healthy controls with 33% sensitivity at 98% specificity (Table 3).
Core Innovation
The invention relates to the identification of 28 antigens as potential biomarkers for the early detection of basal-like breast cancer (BLBC). These biomarkers were selected from screening 10,000 tumor antigens and validated in a blinded study. The invention also includes a 13-autoantibody classifier that differentiates patients with BLBC from healthy controls with 33% sensitivity at 98% specificity. This discovery addresses the need for molecular diagnostic tests to detect BLBC, particularly in women younger than 50 years old, who are not typically recommended for routine mammograms.
The problem solved by this invention arises from the limitations of current breast cancer detection methods such as mammography, which detects only about 70% of breast cancers and has reduced efficacy in detecting BLBC. BLBC is frequently under-diagnosed by routine mammography due to its high proliferation rate and lack of typical suspicious features like microcalcifications. Furthermore, BLBC disproportionately affects younger women who are not recommended for routine mammogram screening, leaving a substantial population without effective early detection options.
This invention exploits the adaptive immune system's generation of autoantibodies against tumor antigens, amplifying signals from minute amounts of tumor proteins present in plasma. Using a nucleic acid programmable protein array (NAPPA) platform, the invention profiles humoral immune responses of BLBC patients to identify subtype-specific autoantibody biomarkers. The 28 identified antigens and the classifier provide a novel molecular diagnostic approach that can be used with plasma samples to detect and diagnose basal-like breast cancer early, overcoming the limitations of existing methods.
Claims Coverage
The patent includes two independent claims focusing on methods for detecting basal-like breast cancer using panels of tumor antigens in plasma or serum samples.
Detection of autoantibodies against a panel of tumor antigens in plasma or serum from female patients under 50 years old
A method comprising contacting a serum or plasma sample from a female patient less than 50 years old to a panel of detectably labeled tumor antigens including P53 (TP53), NYESO1 (CTAG1B), NY ESO2 (CTAG2), and PPHLN1, and detecting binding of at least four tumor antigens with antibodies in the sample at a specificity of at least 97.9%. Detection methods include enzyme-linked immunosorbent assay (ELISA), using a labeled secondary antibody.
Analysis of autoantibodies specific for at least three tumor antigens using ELISA
A method comprising obtaining a serum or plasma sample from a human subject, contacting it to a panel of detectably labeled tumor antigens comprising P53 (TP53), NY-ESO1 (CTAG1B), NY-ESO2 (CTAG2), and PPHLN1, and analyzing for autoantibodies specific for at least three tumor antigens using an enzyme-linked immunosorbent assay. The panel may further include additional tumor antigens such as RNF216, PIP4K2C, ZBTB16, TAS2R8, WBP2NL, and others.
The independent claims cover methods for early detection of basal-like breast cancer by detecting autoantibodies against a specific set of tumor antigens in plasma or serum, using ELISA or similar immunoassays, focusing on female patients under 50 and targeting a defined antigen panel to achieve high specificity and sensitivity.
Stated Advantages
The identified biomarkers enable early detection of basal-like breast cancer even in populations not well served by current screening methods such as younger women under 50 years old.
The use of autoantibodies amplifies detection signals from minute amounts of tumor proteins in plasma, improving sensitivity of molecular diagnostic tests.
The 28 identified antigens and the 13-autoantibody classifier provide a specific molecular signature to differentiate basal-like breast cancer patients from healthy controls with high specificity (98%).
Documented Applications
Early detection and diagnosis of basal-like breast cancer using molecular diagnostic tests based on plasma or serum samples.
Use of autoantibody biomarker panels to detect basal-like breast cancer in female patients less than 50 years old, who would not otherwise be screened effectively by mammography.
Development of diagnostic assays employing enzyme-linked immunosorbent assay (ELISA) formats or nucleic acid programmable protein array (NAPPA) platforms for profiling autoantibody responses against tumor antigen panels.
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