Early detection of breast cancer serum antigens with lambodies

描述(申请人提供)：癌症是全球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，包括乳腺癌，这是女性第二常见的癌症。癌症的早期发现对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。这项建议的目的是利用我们发现的新的糖链结合抗体(Lamprey抗体)，开发一种非侵入性血清生物检测方法，用于乳腺癌的早期检测。LamBody是海鳗特有的富含亮氨酸重复序列的抗体，它能以极高的亲和力和选择性结合多糖，优于大多数凝集素和哺乳动物抗体，后者通常结合多糖的亲和力和/或选择性较差。人类癌细胞表现出异常的糖基化模式，具有许多与正常细胞不同的糖链结构。最广泛使用的癌症生物标记物是体液糖蛋白，它们显示的糖链在肿瘤发生过程中会发生显着变化。这种异常的多糖结构可以作为癌症的诊断和预后生物标记物。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试验缺乏敏感性和特异性。这些生物标记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。我们建议从乳腺癌细胞系中分离出一组比正常更能检测乳腺癌糖蛋白的抗乳腺癌抗体，并使用细胞表面蛋白和条件培养液作为探针。这些抗体将被用来开发一种高灵敏度的夹心ELISA法，用于检测血清糖蛋白中与癌症相关的多糖。我们将对40例乳腺癌患者和40例正常人血清样本的抗体进行初步筛选，以确定检测的特异性和敏感性。这些抗乳腺癌抗体可以预测乳腺癌的风险、诊断和分期、预后和监测治疗反应，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.