Serum Antibody Profiling with a Carbohydrate Microarray

点击翻译按钮获取中文摘要

Biomarkers play a critical role in cancer diagnosis and treatment. 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. In collaboration with Dr. Marjorie Robert-Guroff, we have been profiling immune responses to her HIV/SIV vaccine. We find that immunization with the vaccine does induce anti-glycan antibody responses. We have also been using the array to identify new biomarkers for early detection of cancer and evaluation of prognosis. In collaboration with Drs. Tere Landi, Mei Yin Polley, and Lisa McShane, we have been profiling antibody populations in patients with lung cancer. In collaboration with Drs. Mark Sherman, Mei Yin Polley, and Lisa McShane, we have also been profiling antibody populations in patients with ovarian cancer.