Novel approaches to study immune responses to post translational modifications for cancer detection

研究癌症检测翻译后修饰免疫反应的新方法

基本信息

项目摘要

Project Summary/Abstract Despite advances in screening and treatment, mortalities from breast and lung cancers have remained high in the US over the last 20 years. It is widely accepted that early detection is critical to improving outcomes in both diseases. Both also rely on imaging for screening, but false positive and false negative detection are associated with unnecessary biopsies, missed diagnoses, and costs. There is an urgent need for biochemical markers that improve the performance of imaging technologies. Our laboratories have been successful at identifying useful cancer biomarkers by exploiting patients’ own ability to produce antibodies against tumor- associated antigens (TAA), referred to as tumor-associated autoantibodies (TAAb). With prior EDRN support, we developed high-throughput programmable protein display methods for the rapid detection and validation of autoantibody biomarker signatures in breast and lung cancers. Our breast cancer TAAb biomarkers have been licensed and integrated into Videssa™ Breast that is now available as CLIA-certified test. Our triple negative breast cancer markers have been validated in blinded phase 2 multicenter validation studies. These demonstrate the great utility of TAAb in cancer early detection. However, the sensitivities of most TAAbs is moderate and there is a suggestion that greater sensitivity and specificity could be obtained by examining TAAb directed at aberrantly modified proteins in cancers. Our central hypothesis is that aberrant protein glycosylation, a hallmark of breast and lung cancers, induces glycoprotein-specific TAAb that can be measured as specific serum biomarkers of these cancers. Alterations in glycosylation are highly immunogenic, and there is strong historical evidence for significant antibody responses to cancer-altered glycoproteins. However, all current protein (or polypeptide) display tools allow limited or no post-translational modification. This historical roadblock has prevented the identification of these biomarkers because of the lack of screening methods that test immunogenic structural glycoproteins. We introduce a tool for the high-throughput display of full-length proteins decorated with cancer-specific O-glycan structures. This will revolutionize the opportunity to screen glycan-protein epitopes in their natural context. Our team comprises strong expertise in functional proteomics, biomarker development, glycoproteomics, medical oncology and biostatistics. Targeted proteins will include: the extra-cellular domains of relevant single pass membrane proteins, proteins known to be O-glycosylated and overexpressed in the two cancers, and all known mucins. They will be translated in situ using human ribosomes and chaperone proteins and then systematically decorated with Tn and STn O-GalNAc-type glycans by consecutive addition of recombinant glycosyltransferases and sugar nucleotides to mirror what occurs in the two cancers. Adhering to the principles of PRoBE design, we will screen these arrays with cancer patient and control sera. Our study will focus on cancer patients and non-cancer subjects with positive imaging findings. Study design will include Phase I discovery (arrays/ELISA) and Phase II validation using ELISA.
项目总结/文摘

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Programmable protein arrays for immunoprofiling HPV-associated cancers.
  • DOI:
    10.1002/pmic.201500376
  • 发表时间:
    2016-04
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Ewaisha R;Meshay I;Resnik J;Katchman BA;Anderson KS
  • 通讯作者:
    Anderson KS
Serum autoantibodyome reveals that healthy individuals share common autoantibodies.
  • DOI:
    10.1016/j.celrep.2022.110873
  • 发表时间:
    2022-05-31
  • 期刊:
  • 影响因子:
    8.8
  • 作者:
    Shome, Mahasish;Chung, Yunro;Chavan, Ramani;Park, Jin G.;Qiu, Ji;LaBaer, Joshua
  • 通讯作者:
    LaBaer, Joshua
Proteomic Monitoring of B Cell Immunity.
B 细胞免疫的蛋白质组学监测。
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Karen Sue Anderson其他文献

Karen Sue Anderson的其他文献

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{{ truncateString('Karen Sue Anderson', 18)}}的其他基金

Southwest EDRN Clinical Validation Center for Head and Neck Cancer
西南头颈癌EDRN临床验证中心
  • 批准号:
    10706931
  • 财政年份:
    2023
  • 资助金额:
    $ 18.32万
  • 项目类别:
Biomarker Developmental Laboratory
生物标志物发育实验室
  • 批准号:
    10688271
  • 财政年份:
    2022
  • 资助金额:
    $ 18.32万
  • 项目类别:
Biomarker Developmental Laboratory
生物标志物发育实验室
  • 批准号:
    10487346
  • 财政年份:
    2022
  • 资助金额:
    $ 18.32万
  • 项目类别:
High-throughput immunoproteomics for cancer biomarker discovery
用于癌症生物标志物发现的高通量免疫蛋白质组学
  • 批准号:
    10688268
  • 财政年份:
    2022
  • 资助金额:
    $ 18.32万
  • 项目类别:
Rapid Point of Care Detection of HPV-Associated Malignancies
HPV 相关恶性肿瘤的快速护理点检测
  • 批准号:
    10006505
  • 财政年份:
    2017
  • 资助金额:
    $ 18.32万
  • 项目类别:
Rapid Point of Care Detection of HPV-Associated Malignancies
HPV 相关恶性肿瘤的快速护理点检测
  • 批准号:
    10246794
  • 财政年份:
    2017
  • 资助金额:
    $ 18.32万
  • 项目类别:
Rapid Point of Care Detection of HPV-Associated Malignancies
HPV 相关恶性肿瘤的快速护理点检测
  • 批准号:
    9221542
  • 财政年份:
    2017
  • 资助金额:
    $ 18.32万
  • 项目类别:
Rapid Point of Care Detection of HPV-Associated Malignancies
HPV 相关恶性肿瘤的快速护理点检测
  • 批准号:
    9933545
  • 财政年份:
    2017
  • 资助金额:
    $ 18.32万
  • 项目类别:
Rapid Point of Care Detection of HPV-Associated Malignancies
HPV 相关恶性肿瘤的快速护理点检测
  • 批准号:
    10471927
  • 财政年份:
    2017
  • 资助金额:
    $ 18.32万
  • 项目类别:
Novel approaches to study immune responses to post translational modifications for cancer detection
研究癌症检测翻译后修饰免疫反应的新方法
  • 批准号:
    9355593
  • 财政年份:
    2016
  • 资助金额:
    $ 18.32万
  • 项目类别:

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