Novel immunodiagnostic assays for colorectal cancer detection

用于结直肠癌检测的新型免疫诊断方法

• 批准号: 7611763
• 负责人: CHRISTINE CHAVANY
• 金额: $ 14.15万
• 依托单位: MILAGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-22 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7611763
• 关键词: Accounting; Adenomatous Polyps; Adult; Age; Agreement; Antibodies; Benign; Biological Assay; Biological Markers; Biometry; Breast; Businesses; Cancer Control; Cancer Detection; Cause of Death; Cessation of life; Clinical; Collection; Colon; Colonoscopy; Colorectal; Colorectal Cancer; Commit; Complement; Condition; Data; Detection; Development; Diagnosis; Diagnostic; Disease Management; Diverticulitis; Diverticulosis; Early Detection Research Network; Ensure; Enzyme-Linked Immunosorbent Assay; Excision; Funding; Generations; Genus Cola; Goals; Gold; High Prevalence; Human; Immunoassay; Immunohistochemistry; Immunological Diagnosis; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Invasive; Localized; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Mass Spectrum Analysis; Methods; Michigan; Monoclonal Antibodies; Multivariate Analysis; New England; Numbers; Patient Preferences; Patients; Performance; Phase; Prevalence; Process; Production; Prostate; Protein Array; Protein Sequence Analysis; Proteins; Public Health; ROC Curve; Reagent; Research; Sampling; Screening procedure; Secure; Sensitivity and Specificity; Serum; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Specificity; Specimen; Standards of Weights and Measures; Statistical Data Interpretation; Study Section; Technology; Testing; Tissue Banks; Tissue Sample; Tissues; Translations; Ulcerative Colitis; United States Food and Drug Administration; Universities; Validation; Western Blotting; Woman; Work; assay development; base; blind; cancer type; case control; clinical application; clinical epidemiology; cohort; colon cancer cell line; colorectal cancer screening; cost; innovation; lung cancer screening; men; multidisciplinary; novel; programs; prototype; research study; technology validation; tumor; user-friendly; validation studies

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is the third most common cancer in both men and women, and accounts for almost 10% of all cancer deaths. There are several recommended screening methods for CRC, including colonoscopy and FOBT. Colonoscopy is the current gold standard, yet it is invasive and expensive, and FOBT is not sufficiently sensitive. It is recognized that CRC is curable by resection when localized, however, only 44% of US adults over the age of 50 undergo screening. There is a need for the development of non invasive, more acceptable, yet accurate methods of screening. Our goal is to identify CRC specific serum biomarkers, and to develop and commercialize a serum-based immunodiagnostic assay for CRC detection or screening. We have developed proprietary technologies to identify, validate and develop biomarkers for the detection of major cancers. Our innovative antibody-based approach involves: i) a collection of antibodies raised against known and unknown human proteins; ii) a proprietary protein array referred to as Matrix Protein Array Technology (MPAT) allowing multiplex analysis of a large number of clinical samples using a large number of antibodies; and iii) a collection of tissue and sera specimens from major cancers and controls. In our CRC program, we have identified six CRC tissue specific biomarkers and generated monoclonal antibodies (mAb) that display CRC specificity in tissue samples, as based on MPAT and conventional immunohistochemistry data. In this SBIR Phase I project we propose to test whether the six CRC tissue specific biomarkers are found in patient serum. To this end, we will screen serum samples using the MPAT and the tissue specific mAb against the CRC tissue biomarkers. First we will use small sample sets in pilot experiments, then we will confirm the results in up to 150 CRC and non-CRC serum samples (including benign, inflammatory and normal controls). Statistical analysis of the data points generated in this study will enable us to identify a panel of serum-based biomarkers. Selected biomarkers will be further validated in Phase II, thus leading to the development of an immunodiagnostic assay for CRC detection. The innovative aspects of this proposal are the development of novel biomarkers and novel mAb with clinical applications in CRC detection, and the rapid translation of these products to the patient with the support of clinical collaborators, EDRN validation samples, biostatistics and business consultants. PUBLIC HEALTH RELEVANCE: Colorectal cancer (CRC) is the third most common cancer in both men and women, and the second most common cause of death by cancer in the industrialized world. There are several recommended screening methods for CRC, which are either invasive or not sufficiently sensitive, and only 44% of US adults over 50 undergo screening. A serum-based immunodiagnostic assay for CRC detection or screening would be safer, more cost-effective and user-friendly than currently available methods.

描述（由申请人提供）：结直肠癌（CRC）是男性和女性中第三常见的癌症，占所有癌症死亡的近10%。有几种推荐的CRC筛查方法，包括结肠镜检查和FOBT。结肠镜检查是目前的黄金标准，但它是侵入性的和昂贵的，FOBT不够敏感。据认为，CRC是可治愈的切除时，局部，然而，只有44%的美国成年人超过50岁进行筛选。有必要开发非侵入性的，更可接受的，但准确的筛选方法。我们的目标是鉴定CRC特异性血清生物标志物，并开发和商业化用于CRC检测或筛查的基于血清的免疫诊断测定。我们开发了专有技术来识别、验证和开发用于检测主要癌症的生物标志物。我们创新的基于抗体的方法包括：i）针对已知和未知人类蛋白质的抗体集合; ii）称为基质蛋白质阵列技术（MPAT）的专有蛋白质阵列，允许使用大量抗体对大量临床样本进行多重分析;以及iii）来自主要癌症和对照的组织和血清样本集合。在我们的CRC项目中，我们已经确定了六种CRC组织特异性生物标志物，并根据MPAT和常规免疫组织化学数据生成了在组织样本中显示CRC特异性的单克隆抗体（mAb）。在这个SBIR I期项目中，我们建议测试是否在患者血清中发现六种CRC组织特异性生物标志物。为此，我们将使用MPAT和针对CRC组织生物标志物的组织特异性mAb筛选血清样品。首先，我们将在试点实验中使用小样本集，然后我们将在多达150个CRC和非CRC血清样本（包括良性，炎症和正常对照）中确认结果。本研究中产生的数据点的统计分析将使我们能够识别一组基于血清的生物标志物。选定的生物标志物将在II期进一步验证，从而导致开发用于CRC检测的免疫诊断测定。该提案的创新方面是开发具有CRC检测临床应用的新型生物标志物和新型mAb，以及在临床合作者、EDRN验证样本、生物统计学和业务顾问的支持下将这些产品快速转化为患者。公共卫生相关性：结直肠癌（CRC）是男性和女性中第三常见的癌症，并且是工业化世界中第二常见的癌症死亡原因。有几种推荐的CRC筛查方法，这些方法要么是侵入性的，要么不够敏感，只有44%的50岁以上的美国成年人接受筛查。用于CRC检测或筛查的基于血清的免疫诊断测定将比现有方法更安全，更具成本效益和用户友好。