Lung Cancer Early Detection and Immunotherapy Response Prediction and Monitoring with an Exo-PROS Liquid Biopsy Assay
使用 Exo-PROS 液体活检测定进行肺癌早期检测和免疫治疗反应预测和监测
基本信息
- 批准号:10665754
- 负责人:
- 金额:$ 63.02万
- 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:AddressAntigensArea Under CurveBiological AssayBiological MarkersBiopsyBiosensing TechniquesBiosensorBloodBody FluidsCancer EtiologyCancer PatientCarbohydratesCell CommunicationCell secretionCellsCessation of lifeClinicalComplementConsumptionDataDevelopmentDiagnosticDiagnostic SensitivityDiagnostic testsDiseaseEarly DiagnosisEarly treatmentEnzyme-Linked Immunosorbent AssayEpidermal Growth Factor ReceptorImageImmune checkpoint inhibitorImmunotherapyIn SituMalignant NeoplasmsMalignant neoplasm of lungMeasurementMedical ImagingMethodsMicroRNAsMinorityMonitorNon-Small-Cell Lung CarcinomaNormal CellPatient CarePatient SelectionPatient-Focused OutcomesPatientsPerformancePilot ProjectsPortraitsPrediction of Response to TherapyPredictive ValueProceduresProteinsQuantitative Reverse Transcriptase PCRRNARadiation exposureRisk FactorsSamplingSensitivity and SpecificitySerumSpecificitySurvival RateTechnologyTestingTimeTissuesTumor MarkersTumor-Derivedanti-PD1 therapycancer biomarkerscheckpoint therapyclinical decision-makingcohortcost effectivediagnostic accuracydiagnostic valueeffective therapyexosomeextracellular vesicleshigh riskimaging modalityimprovedliquid biopsylow dose computed tomographylung cancer screeningmortalitynanosizedoverexpressionpembrolizumabpredicting responsepredictive markerprogrammed cell death ligand 1recruitresponders and non-respondersresponsescreeningscreening guidelinessensorsmall cell lung carcinomastandard of careuser-friendly
项目摘要
PROJECT SUMMARY
Lung cancer causes about 25% of all cancer deaths worldwide. Early detection and effective treatment are
critical in reducing the mortality. Low-dose computed tomography (CT) is the recommended screening test for
lung cancer, however, its high false-positive rate leads to unnecessary biopsy and repeated radiation
exposure. Immune checkpoint inhibitors (ICIs) have revolutionized treatment for lung cancer, however, they
are only effective for a minority of patients. Predicting and monitoring responses to ICIs by tissue biopsy and
imaging are limited by invasive procedure, the lack of effective tumor biomarkers, pseudo progression, and
delayed response. Therefore, non-invasive, accurate and affordable methods are urgently needed to detect
lung cancer early and to effectively predict and monitor response to ICIs, aiding in improving patient outcomes.
Liquid biopsy detects tumor-derived biomarkers in body fluids such as blood, complements imaging and risk
factor data, allows sequential monitoring of cancer development, and thus represents a new and non-invasive
strategy to address these unmet needs. Exosomes are nano-sized extracellular vesicles secreted by cells.
They are actively involved in every step of cancer development and have emerged as promising cancer
biomarkers. We hypothesize that tumor-derived exosomes (TEXs) are highly sensitive and specific for lung
cancer early detection and treatment response prediction and monitoring, and the combination of TEX markers
provides superior diagnostic and predictive performances than single markers alone.
A major challenge in developing exosomes-based cancer biomarkers is the separation of TEXs from
exosomes released by normal cells, the latter of which can render the test less sensitive or incapable of
detecting TEX biomarkers. To overcome this challenge, we have developed an exosome protein RNA one stop
(Exo-PROS) biosensor. The Exo-PROS assay first selectively captures TEXs from non-TEXs using cancer-
overexpressed markers, and then, for the first time, provides one-stop and in-situ quantitation of three types of
TEX biomarkers including proteins, microRNAs and carbohydrate antigens. In our pilot study, we demonstrated
that combined TEX biomarkers (EGFR, miR-21, LG3BP, miR-210, TF-Ag-α) distinguished lung cancer from
normal controls with sensitivity of 1.00 and specificity of 1.00. We also showed that TEX PD-L1, miR-21 and
TF-Ag-α successfully predicted the response to anti-PD-1 therapy in lung cancer patients. In this project, we
will (1) further develop the Exo-PROS assay and characterize its analytical performances including sensitivity,
specificity, linear range and repeatability; (2) determine the diagnostic values of Exo-PROS assay in lung
cancer early detection and demonstrate that Exo-PROS assay complements low dose CT and improves the
diagnostic accuracy; (3) evaluate Exo-PROS assay in predicting and monitoring response to anti-PD-1
therapy, and demonstrate that Exo-PROS assay is an effective test to complement tissue biopsy and imaging
modalities in clinical decision making and patient care.
项目摘要
肺癌导致的死亡人数约占全球癌症死亡人数的25%。早期发现和有效治疗是
对降低死亡率至关重要。低剂量计算机断层扫描(CT)是推荐的筛查试验,
然而,肺癌的高假阳性率导致不必要的活检和重复放射治疗
exposure.免疫检查点抑制剂(ICI)已经彻底改变了肺癌的治疗,然而,它们
仅对少数患者有效。通过组织活检预测和监测对ICI的反应,
成像受到侵入性手术、缺乏有效的肿瘤生物标志物、假进展和
延迟响应因此,迫切需要无创、准确、经济实惠的检测方法
肺癌早期,并有效地预测和监测对ICI的反应,帮助改善患者的结果。
液体活检检测体液(如血液)中的肿瘤衍生生物标志物,补充成像和风险
因子数据,允许连续监测癌症发展,因此代表了一种新的非侵入性的方法。
以满足这些未满足的需求。外泌体是由细胞分泌的纳米尺寸的细胞外囊泡。
它们积极参与癌症发展的每一步,并已成为有希望的癌症
生物标志物。我们假设肿瘤来源的外泌体(TEXs)对肺肿瘤的发生具有高度的敏感性和特异性。
癌症的早期检测和治疗反应的预测和监测,以及TEX标志物的组合
提供比单独的单一标志物更好的诊断和预测性能。
开发基于外泌体的癌症生物标志物的主要挑战是将TEX从肿瘤细胞中分离。
由正常细胞释放的外泌体,后者可以使测试不太敏感或不能
检测特克斯生物标志物。为了克服这一挑战,我们开发了一种外泌体蛋白RNA一站式
(Exo-PROS)生物传感器。Exo-PROS检测首先使用癌细胞-癌细胞技术从非TEX中选择性捕获TEX。
过表达的标记,然后,第一次,提供一站式和原位定量的三种类型的
TEX生物标志物包括蛋白质、微小RNA和碳水化合物抗原。在我们的试点研究中,我们证明了
结合TEX生物标志物(EGFR,miR-21,LG3BP,miR-210,TF-Ag-α)区分肺癌和
正常对照的敏感性为1.00,特异性为1.00。我们还发现TEX PD-L1、miR-21和
TF-Ag-α成功预测了肺癌患者对抗PD-1治疗的反应。本课题
将(1)进一步开发Exo-PROS检测试剂盒并表征其分析性能,包括灵敏度,
特异性、线性范围和重复性;(2)确定Exo-PROS检测在肺组织中的诊断价值
癌症早期检测,并证明Exo-PROS检测补充了低剂量CT,并提高了
诊断准确性;(3)评价Exo-PROS检测在预测和监测抗PD-1应答中的作用
Exo-PROS检测是一种有效的检测方法,可补充组织活检和成像
临床决策和患者护理的模式。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('GRACE DY', 18)}}的其他基金
Exosomal Thomsen-Friedenreich glycoantigen as a new biomarker for lung cancer screening and early detection
外泌体 Thomsen-Friedenreich 糖抗原作为肺癌筛查和早期检测的新生物标志物
- 批准号:
10670439 - 财政年份:2022
- 资助金额:
$ 63.02万 - 项目类别:
Exosomal Thomsen-Friedenreich glycoantigen as a new biomarker for lung cancer screening and early detection
外泌体 Thomsen-Friedenreich 糖抗原作为肺癌筛查和早期检测的新生物标志物
- 批准号:
10511082 - 财政年份:2022
- 资助金额:
$ 63.02万 - 项目类别:
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