Antigen binding molecules for small cell lung cancer
Inventors
Lampe, Paul • McGarry Houghton, Ashley • Lastwika, Kristin
Assignees
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Publication Number
US-12344653-B2
Publication Date
2025-07-01
Expiration Date
Abstract
Small cell lung cancer specific chimeric antigen receptor comprising: an antigen-binding domain capable of specifically binding an antigen selected from Tables 1A, 1B, 2A, 2B and 4 and/or that specifically binds to or interacts GAD65, PTPRU, TFRC and GABA-b. A method for treating a subject suffering from SCLC comprising, introducing into the subject a therapeutically effective amount of a T lymphocyte comprising a chimeric antigen receptor. An antigen binding molecule, comprising: an antigen-binding domain capable of specifically binding an antigen selected from Tables 1A, 1B, 2A, 2B and 4 and/or that specifically binds to or interacts GAD65, PTPRU, TFRC and GABA-b. A method of detecting an SCLC tumor in a subject.
Core Innovation
The invention provides a plasma-based, highly multiplexed hybrid biomarker platform for early detection and classification of limited stage small cell lung cancer (SCLC). It uses a diagnosis workflow that interrogates circulating autoantibodies capable of binding, respectively, to four specified targets related to GAD65, PTPRU, TFRC, and GABA-b.
The core technical approach is a biomarker detection array configured to assay four autoantibodies, anti-GAD65, anti-PTPRU, anti-TFRC, and anti-GABA-b, or, alternatively, four antigen-autoantibody complexes, GAD65-autoantibody complex, PTPRU-autoantibody complex, TFRC-autoantibody complex, and GABA-b-autoantibody complex. Limited stage SCLC or SCLC is diagnosed when the amount of each of the four measured species in the biological sample exceeds, respectively, a control amount.
The invention also provides a biomarker detection array for limited stage SCLC that consists essentially of antibodies capable of specifically binding, respectively, to the four antigen-autoantibody complexes. The disclosed supporting context states that CNS-directed autoantibodies/complexes are frequently present in SCLC patients even without paraneoplastic syndromes (PNS).
Claims Coverage
The independent claims cover three related aspects: treating limited stage SCLC based on array-based diagnosis using four autoantibodies; treating limited stage SCLC based on array-based diagnosis using four antigen-autoantibody complexes; and the biomarker detection array itself. The main inventive focus is on the four-target array/measurement and using exceedance of respective control amounts as the diagnosis basis.
Treating limited stage SCLC using four autoantibodies measured on an antigen array
A method of treating small cell lung cancer in a subject diagnosed with limited stage SCLC, where the subject is diagnosed by contacting a biological sample with an array consisting essentially of antigens capable of specifically binding respectively to four autoantibodies (anti-GAD65, anti-PTPRU, anti-TFRC, and anti-GABA-b), detecting an amount of the four autoantibodies when the autoantibodies bind to the antigens in the array, and diagnosing limited stage SCLC when the amount of the four autoantibodies exceeds, respectively, a control amount.
Treating limited stage SCLC using four antigen-autoantibody complexes measured on an antibody array
A method of treating small cell lung cancer in a subject diagnosed with limited stage SCLC, where the subject is diagnosed by contacting a biological sample with an array consisting essentially of antibodies capable of specifically binding respectively to four antigen-autoantibody complexes (GAD65-autoantibody complex, PTPRU-autoantibody complex, TFRC-autoantibody complex, and GABA-b-autoantibody complex), detecting an amount of the four complexes when the complexes bind to the antibodies in the array, and diagnosing SCLC when the amount of the four complexes exceeds, respectively, a control amount.
Biomarker detection array consisting essentially of antibodies to four antigen-autoantibody complexes
A biomarker detection array for limited stage small cell lung cancer consisting essentially of antibodies capable of specifically binding, respectively, to four antigen-autoantibody complexes, wherein the four antigen-autoantibody complexes are a GAD65-autoantibody complex, a PTPRU-autoantibody complex, a TFRC-autoantibody complex, and a GABA-b-autoantibody complex.
Together, the independent claims define a diagnosis-driven treatment framework for limited stage SCLC and a corresponding biomarker detection array. The claims center on detecting either four autoantibodies or four antigen-autoantibody complexes using an array that consists essentially of specifically binding antigen/antibody components, followed by diagnosis when the detected amounts exceed respective control amounts.
Stated Advantages
Plasma-based, highly multiplexed hybrid biomarker platform for early detection and classification of limited stage small cell lung cancer (SCLC).
CNS-directed autoantibodies/complexes are frequently present in SCLC patients even without paraneoplastic syndromes (PNS).
Validation across multiple independent cohorts, with performance metrics for specific markers and combined marker panels, and assay reproducibility evidence.
Documented Applications
Diagnosis of limited stage small cell lung cancer (SCLC).
Classification of limited stage small cell lung cancer (SCLC).
Treatment of a subject diagnosed with limited stage SCLC by administering a chemotherapy regimen or an immunotherapy regimen.
Immunotherapy embodiments include engineered human T cells expressing a chimeric antigen receptor that binds an antigen selected from GAD65, PTPRU, TFRC, and GABA-b.
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