Early detection of breast cancer serum antigens with lambodies

用lambody早期检测乳腺癌血清抗原

• 批准号: 8619768
• 负责人: LI MAO
• 金额: $ 16.69万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-03 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8619768
• 关键词: Affinity; Antibodies; Antigens; Binding; Biological Assay; Biological Markers; Blood; Body Fluids; Breast Cancer Cell; Breast Cancer Detection; Breast Cancer Early Detection; Cancer Detection; Cancer Diagnostics; Cancer Etiology; Cancer cell line; Cell Surface Proteins; Cessation of life; Clinical; Conditioned Culture Media; Data; Detection; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease remission; Distant; Drops; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Evaluation; Foundations; Glycoproteins; Goals; Human; Intervention; Lampreys; Lectin; Leucine-Rich Repeat; Libraries; Malignant Neoplasms; Membrane Glycoproteins; Monitor; Normal Cell; Organ; Patients; Pattern; Performance; Petromyzon marinus; Polysaccharides; Prognostic Marker; Prospective Studies; Reagent; Research Design; Sampling; Screening for cancer; Sensitivity and Specificity; Serum; Specificity; Staging; Structure; Surface; Survival Rate; Testing; Therapeutic; United States; Woman; Yeasts; base; cancer cell; cancer diagnosis; cancer risk; cancer type; combinatorial; glycosylation; malignant breast neoplasm; neoplastic cell; novel; outcome forecast; prognostic; public health relevance; response; tumor; tumorigenesis

DESCRIPTION (provided by applicant): Cancer is a leading cause of human death worldwide, yet there are no early detection assays available for the majority of cancer types, including breast cancer that is the second most prevalent cancer in women. Early detection of cancer is vital for successful clinical intervention, as rates of remission drop sharply at advance stages of the disease. The objective of this proposal is to develop a noninvasive serum bioassay for early detection of breast cancer using the novel glycan-binding lambodies (lamprey antibodies) we discovered. Lambodies are the unique leucine-rich repeat-based antibodies of sea lamprey, which can bind glycans with exquisite affinity and selectivity, superior to that of most lectins and mammalian antibodies, which typically bind glycans with poor affinity and/or selectivity. Human cancer cells display aberrant glycosylation patterns, with many glycan structures different from those in normal cells. The most widely used cancer biomarkers are body-fluid glycoproteins and the glycans they display can change markedly during oncogenesis. Such aberrant glycan structures could serve as diagnostic and prognostic cancer biomarkers. However, due to the poor affinity and/or selectivity for glycans of most conventional reagents, current clinical cancer diagnostic tests lack sensitivity and specificity. These biomarkers are often useful only after the disease has been diagnosed, usually at late stages when the cancer has spread to distant organs. We propose to isolate a panel of anti-breast cancer lambodies that can preferentially detect breast cancer glycoproteins compared to normal, using as probes cell-surface proteins and conditioned medium from breast cancer cell lines. These lambodies will be used develop a highly sensitive sandwich-ELISA test for detection of cancer-associated glycans in serum glycoproteins. A pilot screen will be performed with the lambodies on 40 breast cancer and 40 normal human serum samples, to determine the specificity and sensitivity of the assays. These anti-breast cancer lambodies may enable prediction of breast cancer risk, diagnosis and staging, prognosis and monitoring the response to therapy, which could have a major impact on the survival of patients.

描述（由申请人提供）：癌症是全世界人类死亡的主要原因，但目前还没有针对大多数癌症类型的早期检测方法，包括女性第二大常见癌症的乳腺癌。癌症的早期发现对于成功的临床干预至关重要，因为在疾病的晚期阶段缓解率急剧下降。该提案的目的是利用我们发现的新型聚糖结合lambody（七鳃鳗抗体）开发一种非侵入性血清生物测定法，用于乳腺癌的早期检测。 Lambodies 是海七鳃鳗独特的富含亮氨酸重复序列的抗体，它可以以精湛的亲和力和选择性结合聚糖，优于大多数凝集素和哺乳动物抗体，后者通常以较差的亲和力和/或选择性结合聚糖。人类癌细胞表现出异常的糖基化模式，许多聚糖结构与正常细胞中的不同。最广泛使用的癌症生物标志物是体液糖蛋白，它们显示的聚糖在肿瘤发生过程中会发生显着变化。这种异常的聚糖结构可以作为诊断和预后癌症生物标志物。然而，由于大多数常规试剂对聚糖的亲和力和/或选择性较差，目前的临床癌症诊断测试缺乏敏感性和特异性。这些生物标志物通常只有在疾病被诊断出来后才有用，通常是在癌症扩散到远处器官的晚期。 我们建议使用来自乳腺癌细胞系的细胞表面蛋白和条件培养基作为探针，分离出一组抗乳腺癌lambody，与正常细胞相比，它们可以优先检测乳腺癌糖蛋白。这些lambody将用于开发一种高度灵敏的夹心ELISA测试，用于检测血清糖蛋白中与癌症相关的聚糖。将使用lambody对 40 份乳腺癌和 40 份正常人血清样本进行初步筛选，以确定检测的特异性和敏感性。这些抗乳腺癌lambody可以预测乳腺癌风险、诊断和分期、预后以及监测治疗反应，这可能对患者的生存产生重大影响。