Serum Antibody Profiling with a Carbohydrate Microarray

生物标志物在癌症诊断和治疗中起着关键作用。血清抗体代表一类重要的生物标志物，具有许多有利的特征，例如良好的稳定性、在生物流体中的可接近性和易于检测。已经有了广泛的研究，以确定蛋白质抗原的抗体水平的变化;然而，结合碳水化合物抗原的抗体的分析在很大程度上没有得到充分利用。我们的碳水化合物微阵列非常适合于监测人类血清中抗聚糖抗体的库，并研究其水平对疾病或疾病治疗的反应。高通量方法可用于鉴定新的单一生物标志物或鉴定可用作生物标志物的变化或概况的组合。在过去的几年里，我们已经开发和验证了碳水化合物微阵列测定用于测量人血清中的抗体水平。现在，我们正在将这项技术应用于各个领域。与Schlom博士及其同事合作，我们一直在使用该阵列评估对PSA-TRICOM前列腺癌疫苗（PROSTVAC-VF）的免疫反应。我们发现，接种前A型血三糖IgM抗体水平与PROSTVAC-VF的存活率相关。此外，我们发现对Forssman抗原的抗体应答与总生存期相关。这两种相关性在两个独立的患者组中是一致的，包括100多名患者。这些是有希望的新生物标志物，用于确定哪些患者应该接受PROSTVAC-VF，以及哪些接受PROSTVAC-VF的患者具有良好的免疫应答。最后，与Elizabeth Jaffee合作，我们分析了GVAX胰腺全细胞疫苗诱导的免疫应答。

Biomarkers play a critical role in cancer diagnosis and treatment. Serum antibodies represent an important class of biomarkers with many advantageous features such as good stability, accessibility in biofluids, and easy detection. There has been extensive research on identifying changes in antibody levels to protein antigens; however, analysis of antibodies that binding carbohydrate antigens have been largely underutilized. Our carbohydrate microarray is well-suited to monitor the repertoire of anti-glycan antibodies in human serum and to study changes in their levels in response to disease or treatment of disease. The high-throughput approach can be used to identify new single biomarkers or to identify combinations of changes or profiles that are useful as biomarkers. Over the last few years, we have developed and validated a carbohydrate microarray assay for measuring antibody levels in human serum. We are now applying this technology in a variety of areas. In collaboration with Dr. Schlom and colleagues, we have been using the array to evaluate immune responses to the PSA-TRICOM prostate cancer vaccine (PROSTVAC-VF). We have found the pre-vaccination IgM antibody levels to blood group A trisaccharide correlate with survival on PROSTVAC-VF. In addition, we have found that antibody response to the Forssman antigen correlate with overall survival. Both correlations are consistent in two independent patient groups encompassing over 100 patients. These are promising new biomarkers for determining which patients should receive PROSTVAC-VF and which patients on PROSTVAC-VF are having a favorable immune response. Finally, in collaboration with Elizabeth Jaffee, we have profiled immune responses induced by GVAX Pancreas whole cell vaccine.