Early detection of breast cancer serum antigens with lambodies

描述（由申请人提供）：癌症是全球人类死亡的主要原因，但大多数癌症类型（包括女性第二大流行癌症乳腺癌）没有早期检测方法。癌症的早期检测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。本提案的目的是开发一种非侵入性的血清生物测定乳腺癌的早期检测使用新的聚糖结合lambodies（七鳃鳗抗体），我们发现。Lambodies是独特的富含亮氨酸的基于重复序列的海七鳃鳗抗体，其可以以精确的亲和力和选择性结合聚糖，其上级于大多数凝集素和哺乳动物抗体的亲和力和选择性，其通常以差的亲和力和/或选择性结合聚糖。人类癌细胞显示异常糖基化模式，其中许多聚糖结构不同于正常细胞中的那些。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期间会发生显著变化。这种异常的聚糖结构可以作为诊断和预后癌症的生物标志物。然而，由于大多数常规试剂对聚糖的亲和力和/或选择性差，目前的临床癌症诊断测试缺乏灵敏度和特异性。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。 我们建议分离出一组抗乳腺癌的lambodies，可以优先检测乳腺癌糖蛋白相比，正常的，作为探针的细胞表面蛋白和条件培养基从乳腺癌细胞系。这些单克隆抗体将用于开发用于检测血清糖蛋白中的癌症相关聚糖的高灵敏度ELISA检测。将对40份乳腺癌和40份正常人血清样本进行初步筛选，以确定测定的特异性和灵敏度。这些抗乳腺癌lambodies可以预测乳腺癌风险，诊断和分期，预后和监测对治疗的反应，这可能对患者的生存产生重大影响。

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.