Serum Antibody Profiling with a Carbohydrate Microarray

生物标志物在癌症的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，具有稳定性好、在生物体液中可及、易检测等优点。对蛋白质抗原抗体水平的变化进行了广泛的研究；然而，对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的抗糖抗体谱系，并研究它们在应对疾病或疾病治疗时水平的变化。高通量方法可用于识别新的单一生物标记物，或识别作为生物标记物有用的变化或概况的组合。在过去的几年里，我们已经开发并验证了一种用于测量人血清抗体水平的碳水化合物微阵列检测方法。我们现在正在将这项技术应用于各种领域。在与Schlom博士和同事的合作下，我们一直在使用该阵列来评估PSA-Tricom前列腺癌疫苗(Prostvac-VF)的免疫应答。我们发现疫苗接种前抗A血型三糖的IgM抗体水平与前列腺癌VF的存活率有关。此外，我们还发现对Forssman抗原的抗体反应与总存活率相关。这两种相关性在涵盖100多名患者的两个独立患者组中是一致的。这些都是很有希望的新的生物标志物，可以确定哪些患者应该接受Prostvac-VF治疗，哪些患者在接受Prostvac-VF治疗时有良好的免疫反应。最后，我们与伊丽莎白·贾菲合作，分析了GVAX胰腺全细胞疫苗诱导的免疫反应。我们还开始研究SARS-CoV-2感染诱导的碳水化合物抗原的抗体反应。

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. We also began studying antibody responses to carbohydrate antigens induced by SARS-CoV-2 infection.