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
基本信息
- 批准号:10688268
- 负责人:
- 金额:$ 96.22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:ART proteinAcademic Medical CentersAddressAdoptionAntibodiesAutoantibodiesAutoantigensB-Lymphocyte EpitopesB-LymphocytesBenignBindingBiological AssayBiological MarkersBlindedBlood TestsBostonBreastCLIA certifiedCancer CenterCancer ControlCancer DetectionCancer PatientCancer VaccinesCarcinogenesis MechanismClinicalCollaborationsCollectionComplementDataDevelopmentDiagnosticDiseaseEarly Detection Research NetworkEarly DiagnosisEnvironmentEnzyme-Linked Immunosorbent AssayEpitopesFundingFutureGenesGerman populationGlycoproteinsGoalsHeterogeneityHumanHuman PapillomavirusImageImmuneImmune SeraImmune responseImmunityImmunoassayImmunoglobulin GImmunologic MarkersImmunologyIndividualLaboratoriesLengthLung noduleMalignant - descriptorMalignant NeoplasmsMalignant neoplasm of lungMalignant neoplasm of ovaryMeasuresMethodsMigration AssayMonitorMorbidity - disease rateMutationNCI Center for Cancer ResearchNoduleNucleic AcidsOvarianPersonsPhasePhase III Clinical TrialsPlasmidsPolysaccharidesPost-Translational Protein ProcessingPredictive ValueProductionProtein ArrayProtein GlycosylationProteinsProteomeProteomicsReproducibilitySamplingScreening for Ovarian CancerScreening for cancerSerologySerology testSerumSpecificitySpeedStructural ProteinStructureSymptomsSystemTechnologyTumor AntigensUniversitiesVaccine DesignVaccinesValidationantimicrobialassay developmentbasebiomarker discoverybiomarker panelbiomarker signaturecancer biomarkerscancer diagnosiscandidate markercirculating biomarkersclinical applicationclinical assay developmentclinical diagnosisclinical diagnosticsclinical implementationcoronavirus diseasedensitydesigndiagnostic platformdisease heterogeneityexperienceglycosylationglycosyltransferaseimmunogenicimmunogenicityimprovedimproved outcomeinnovationinstrumentlung cancer screeningmicrobialmicroorganism antigenmigrationmortalitymultiplex assaynoveloperationpolypeptidepreventprotein biomarkersprotein expressionprotein structurerapid detectionrapid techniquerepositoryrespiratory pathogenscreeningserological markerskillsspecific biomarkersstructural glycoproteintechnology developmenttumorvalidation studies
项目摘要
Project Summary/Abstract
The goal of the ASU Biomarker Characterization Center is to improve ovarian and lung cancer screening through
the development of biologically-relevant circulating immune biomarkers. The scientific approach of our Center is
based on several fundamental principles. First, that altered cancer protein expression, structure, and post-
translational modifications induce host autoantibodies to create circulating biomarkers. Second, that alterations
in microbial antigen expression (such as respiratory pathogens) also induce immunity, often detected in benign
rather than malignant disease. Third, that the protein modifications, as well as the immune response to these
neoantigenic structures, are heterogeneous between people, and that serologic biomarkers may complement
circulating protein biomarkers. We will take a systems immunology approach to discover three types of
antibodies, anti-microbial antibodies, autoantibodies and anti-aberrant glycoprotein antibodies. Our proposal
builds on our extensive experiences with cancer biomarker discovery and immunoproteomics technology
development. Our previous results on autoantibody biomarkers have been confirmed in blinded phase 2
multicenter validation studies and led to a CLIA-certified commercial blood test. Our results have shown that
multiplexed panels of autoantibodies are required for adequate predictive value. With prior EDRN support, we
have developed a set of innovative immunoproteomics technologies, namely high-density nucleic acid
programmable protein array (HD-NAPPA), contra-capture protein array (CCPA) and multiplexed in solution
protein array (MISPA), that, together with the largest full-length human and microbial gene collection at our
DNASU plasmid repository, enable us to study antibodies against the full human proteome, microbial proteomes
and the human O-glycoproteome for antibody biomarker signatures in cancer. Our Meso Scale Diagnostics
(MSD) team has fielded over 3,000 instruments worldwide, and over 700 commercially available biomarker assay
kits. Our expertise at serologic assay development was selected by Operation Warp Speed to use the V-PLEX®
serology panels as the basis of its standard binding assays for immunogenicity assessments in all funded Phase
III clinical trials of COVID vaccines. We will use our MSD MultiArray platform to migrate the top serologic and
protein markers for their utility in our target clinical applications. We will collaborate with experts on lung and
ovarian cancer screening at Vanderbilt University Medical Center, Boston University, MD Anderson Cancer
Center, and German Cancer Research Center, who will also provide access to high-quality well-characterized
samples to develop circulating biomarkers to enhance ovarian cancer screening or to distinguish benign from
malignant pulmonary nodules. Adhering to the principles of PRoBE design, we will perform Phase I discovery by
screening protein arrays with cancer patient and control sera for cancer or control-specific antibodies. Candidate
biomarkers for both lung and ovarian cancers will undergo Phase 2 validation.
项目总结/摘要
亚利桑那州立大学生物标志物表征中心的目标是改善卵巢癌和肺癌筛查,
生物学相关的循环免疫生物标志物的开发。我们中心的科学方法是
基于几个基本原则。首先,这改变了癌蛋白的表达、结构和后
翻译修饰诱导宿主自身抗体产生循环生物标志物。第二,改变
在微生物抗原表达(如呼吸道病原体)也诱导免疫,通常在良性
而不是恶性疾病。第三,蛋白质的修饰,以及免疫反应,
新抗原结构在人与人之间是异质的,血清学生物标志物可以补充
循环蛋白质生物标志物。我们将采用系统免疫学方法来发现三种类型的
抗体、抗微生物抗体、自身抗体和抗异常糖蛋白抗体。我们的建议
基于我们在癌症生物标志物发现和免疫蛋白质组学技术方面的丰富经验
发展我们先前关于自身抗体生物标志物的结果已在盲态2期试验中得到证实
多中心验证研究,并导致CLIA认证的商业血液测试。我们的研究结果表明,
需要多重自身抗体组以获得足够的预测值。在EDRN的支持下,我们
开发了一套创新的免疫蛋白质组学技术,即高密度核酸
可编程蛋白质阵列(HD-NAPPA)、反向捕获蛋白质阵列(CCPA)和溶液中的多重
蛋白质阵列(MISPA),连同我们最大的全长人类和微生物基因收集,
DNASU质粒库,使我们能够研究抗体对全人类蛋白质组,微生物蛋白质组
和人O-糖蛋白质组用于癌症中的抗体生物标志物特征。中尺度诊断
(MSD)该团队已在全球部署了3,000多台仪器,以及700多个商业生物标志物测定
套件我们在血清学检测开发方面的专业知识被Operation Warp Speed选择使用V-PLEX®
在所有受资助的阶段中,血清学样本组作为免疫原性评估的标准结合试验的基础
三、新型冠状病毒疫苗临床试验。我们将使用我们的MSD MultiArray平台迁移顶级血清学和
蛋白质标记物在我们的目标临床应用中的效用。我们将与肺部专家合作,
范德比尔特大学医学中心的卵巢癌筛查,波士顿大学,MD安德森癌症
中心和德国癌症研究中心,谁也将提供获得高质量的良好特点,
样本开发循环生物标志物,以加强卵巢癌筛查或区分良性和恶性卵巢癌。
恶性肺结节遵循PRoBE设计的原则,我们将通过以下方式执行第一阶段发现:
用癌症患者和对照血清筛选蛋白质阵列中的癌症或对照特异性抗体。候选
肺癌和卵巢癌的生物标志物将进行2期验证。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Comparative Microbiomics Analysis of Antimicrobial Antibody Response between Patients with Lung Cancer and Control Subjects with Benign Pulmonary Nodules.
- DOI:10.1158/1055-9965.epi-22-0384
- 发表时间:2023-04-03
- 期刊:
- 影响因子:0
- 作者:
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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:
$ 96.22万 - 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:
$ 96.22万 - 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:
$ 96.22万 - 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:
$ 96.22万 - 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:
$ 96.22万 - 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:
$ 96.22万 - 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:
10463894 - 财政年份:2016
- 资助金额:
$ 96.22万 - 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:
$ 96.22万 - 项目类别:
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