Serum Antibody Profiling with a Carbohydrate Microarray

生物标志物在癌症诊断和治疗中起着至关重要的作用。血清抗体是一类重要的生物标志物，具有良好的稳定性、易获得性和易于检测等优点。在识别蛋白质抗原的抗体水平变化方面已经进行了广泛的研究；然而，结合碳水化合物抗原的抗体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监测人类血清中的抗聚糖抗体，并研究其水平在疾病反应或疾病治疗中的变化。高通量方法可用于识别新的单一生物标记物或识别可用作生物标记物的变化或概况的组合。在过去的几年中，我们开发并验证了一种碳水化合物微阵列测定法，用于测量人类血清中的抗体水平。我们现在正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来评估对PSA-TRICOM前列腺癌疫苗（PROSTVAC-VF）的免疫反应。我们发现疫苗接种前针对A型三糖的IgM抗体水平与PROSTVAC-VF的存活相关。此外，我们发现抗体对福斯曼抗原的反应与总生存率相关。这两种相关性在两个独立的超过100例患者组中是一致的。这些都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，哪些患者接受PROSTVAC-VF具有良好的免疫反应。最后，我们与Elizabeth Jaffee合作，研究了GVAX胰腺全细胞疫苗诱导的免疫反应。

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.