Early detection of breast cancer serum antigens with lambodies

描述（由申请人提供）：癌症是世界范围内人类死亡的主要原因，但大多数癌症类型都没有早期检测方法，包括乳腺癌，这是妇女中第二大常见癌症。早期发现癌症对于成功的临床干预至关重要，因为在疾病的晚期，缓解率会急剧下降。本提案的目的是开发一种无创血清生物测定法，用于使用我们发现的新型聚糖结合板抗体（七鳃鳗抗体）进行乳腺癌的早期检测。七鳃鳗抗体是海七鳃鳗特有的富含亮氨酸的重复基抗体，它能以极好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，后者通常结合亲和力和/或选择性较差的聚糖。人类癌细胞表现出异常的糖基化模式，许多糖基结构与正常细胞不同。最广泛使用的癌症生物标志物是体液糖蛋白，它们所显示的聚糖在肿瘤发生过程中会发生显著变化。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多糖的亲和力和/或选择性较差，目前的临床癌症诊断检测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之后才有用，通常是在癌症扩散到远处器官的晚期。我们提出从乳腺癌细胞系中分离出一组抗乳腺癌lambodies，该lambodies可以优先检测乳腺癌糖蛋白，而不是正常的，使用细胞表面蛋白和条件培养基作为探针。这些lambody将用于开发一种高灵敏度的三明治- elisa检测血清糖蛋白中癌症相关聚糖。将对40个乳腺癌和40个正常人血清样本进行试验性筛选，以确定检测的特异性和敏感性。这些抗乳腺癌抗体可以预测乳腺癌的风险、诊断和分期、预后以及监测对治疗的反应，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.