Development of an Angiogenic T Cell Assay for Personalized Cytomics in Cardiovasc

心血管个性化细胞组学血管生成 T 细胞测定的开发

• 批准号: 8645092
• 负责人: Todd Johnson
• 金额: $ 22.29万
• 依托单位: CYTOVAS, LLC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8645092
• 关键词: Accounting; Activities of Daily Living; Adult; Adverse effects; Aging; Algorithms; Antibodies; Atherosclerosis; Biological Assay; Biological Markers; Blood Tests; Blood Vessels; CD3 Antigens; CXCR4 gene; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular system; Caring; Cell Proliferation; Cell physiology; Cells; Cholesterol; Clinic; Clinical; Clinical assessments; Collection; Color; Communities; Computer Analysis; Computing Methodologies; Data; Developing Countries; Development; Diabetes Mellitus; Diagnostic; Diet; Disease; Endothelial Cells; Environment; Environmental Risk Factor; Evaluation; Flow Cytometry; Funding; Genetic; Genetic Risk; Genomics; Goals; Habits; Health; Health Status; Healthcare; Heart; High Prevalence; Hypertension; In Vitro; Individual; Laboratories; Measurement; Measures; Methods; Modeling; Morbidity - disease rate; Obesity; Oncogenic; Outcome; PECAM1 gene; Pathology; Patients; Pattern; Pharmacologic Substance; Phenotype; Population; Preparation; Prevalence; Prevention; Preventive; Preventive Intervention; Process; Proteomics; Protocols documentation; Research; Risk; Risk Assessment; Risk Factors; Running; Sampling; Sensitivity and Specificity; Stem cells; Stratification; Symptoms; T-Lymphocyte; Testing; Therapeutic; Time; Toxic effect; Tube; United States National Institutes of Health; Vascular System; angiogenesis; base; cardiovascular disorder risk; cardiovascular risk factor; combinatorial; data acquisition; diabetic; drug development; improved; mortality; novel; peripheral blood; public health relevance; response; standard of care; therapeutic effectiveness; tool

DESCRIPTION (provided by applicant): The goal of this research is to develop a new flow cytometry-based test for the clinical measurement of proangiogenic T cells. Such an assay does not exist today. Proangiogenic T cells, including angiogenic T cell (Tang) and Th17 subsets, participate in reparative mechanisms in the vasculature, in oncogenic angiogenesis and in other processes central to the overall health of the vascular system. The T cell test could be deployed as a stand-alone diagnostic tool but will ultimately provide the final core module of the Cytometric Vascular Health Profile (CytoVasHP), a cell-based blood test for the assessment of vascular health. The cardiovascular community has realized that patients who present with similar risk of cardiovascular disease often end up developing (or not) a range of pathologies with different morbidity, mortality and responses to therapy. To determine the most effective care for individual patients and to identify those most likely to benefit from specific interventios for prevention or treatment, there is an urgent need for new methods and tools that can account for individual patient differences and provide a comprehensive measurement of vascular health status. The addition of this new assay to the CytoVasHP will substantially increase the information potential of the profile. Millions of people worldwide could benefit from the development of the CytoVasHP. Cardiovascular disease (CVD) prevalence in the USA is 37% among adults and is projected to increase by 10% over the next 20 years. CVD risk factors such as obesity, hypertension and diabetes have a high prevalence worldwide, exacerbated by aging populations in the developed world and by changing diets and cultural habits in the developing countries. CytoVasHP is a multicomponent clinical assay that will integrate a number of cellular biomarkers of genetic and environmental risk factors (including vascular microparticles (MPs) and endothelial progenitor cells (EPCs)) with a unique and powerful pattern-discerning computational method. Measurement of proangiogenic Tang and Th17 will be a core component of the comprehensive measure of vascular health offered by CytoVasHP. The test will use flow cytometry and biocomputation to yield the CytoVasHP, which could be deployed in the drug development environment to inform pharmaceutical companies of potential vascular benefits or toxicities of new candidate therapeutics. Ultimately, the CytoVasHP will be ordered in the clinic for asymptomatic individuals being considered for cardiovascular preventive treatment, for assessing therapeutic effectiveness in patients being treated with cardiovascular drugs, or to assess cardiovascular toxicities as a side effect of other therapies. This project will develop a single tube flow cytometric panel to quantify proangiogenic T cells, Tang and Th17, composed of CD3, CD4, CD31, KDR, Il23R, CD 161, and CD184 (CXCR4) measurements. Laboratory protocols for sample preparation and data acquisition will be combined with the refinement and adaptation of a high dimensional computational approach for clinical interpretive analysis.

描述（由申请人提供）：本研究的目标是开发一种新的基于流式细胞术的检测方法，用于临床测量促血管生成T细胞。今天不存在这样的分析。促血管生成T细胞，包括血管生成T细胞（Tang）和Th17亚群，参与脉管系统中的修复机制、致癌性血管生成和对血管系统的整体健康至关重要的其他过程。T细胞检测可以作为一种独立的诊断工具部署，但最终将提供细胞计量血管健康概况（CytoVasHP）的最终核心模块，这是一种基于细胞的血液检测，用于评估血管健康。心血管界已经意识到，具有相似心血管疾病风险的患者通常最终会发展（或不发展）一系列具有不同发病率、死亡率和治疗反应的病理。为了确定对个体患者最有效的护理，并确定那些最有可能受益于特定干预措施的预防或治疗，迫切需要新的方法和工具，可以解释个体患者的差异，并提供全面的测量血管健康状况。CytoVasHP中添加这种新检测试剂盒将大大增加该图谱的信息潜力。全世界数百万人可以从CytovasHP的开发中受益。美国成年人心血管疾病（CVD）患病率为37%，预计未来20年将增加10%。肥胖、高血压和糖尿病等心血管疾病风险因素在全球范围内的患病率很高，发达国家的人口老龄化以及发展中国家不断变化的饮食和文化习惯加剧了这一问题。CytoVasHP是一种多组分临床检测方法，将遗传和环境风险因素（包括血管微粒（MP）和内皮祖细胞（EPC））的许多细胞生物标志物与独特而强大的模式识别计算方法相结合。测量促血管生成Tang和Th17将是CytoVasHP提供的血管健康综合测量的核心组成部分。该测试将使用流式细胞术和生物计算来产生CytoVasHP，它可以部署在药物开发环境中，以告知制药公司新候选疗法的潜在血管益处或毒性。最终，CytoVasHP将在临床上用于考虑进行心血管预防治疗的无症状个体，用于评估接受心血管药物治疗的患者的治疗效果，或评估作为其他治疗副作用的心血管毒性。本项目将开发一种单管流式细胞仪，用于定量促血管生成T细胞（Tang和Th17），包括CD 3、CD 4、CD 31、KDR、IL 23 R、CD 161和CD 184（CXCR 4）测量值。样本制备和数据采集的实验室方案将与临床解释分析的高维计算方法的改进和适应相结合。