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. We have developed and validated a carbohydrate microarray assay for measuring antibody levels in human serum. We have used the array to characterize the natural collection of antibodies in healthy individuals and to evaluate relationships between covariates and antibody levels. We have found no significant differences based on gender, race, or geographic location. However, statistically significant differences were associated with blood type and age. In addition, we have evaluated changes within individuals over time and found that antibody levels are stable over periods of 3-13 weeks. This information is critical for identifying changes that are beyond the natural level of variation. In collaboration with Dr. Schlom and colleagues, we have been using the array to evaluate immune responses to the PSA-TRICOM prostate cancer vaccine. In addition, we have evaluated responses to keyhole limpet hemocyanin (KLH), an immunotherapeutic agent used to prevent recurrence of bladder cancer after surgery. We have recently started a project with Dr. Marjorie Robert-Guroff to profile immune responses to her HIV/SIV vaccine.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011055-03
Application #
8157603
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2010
Total Cost
$459,103
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Scheepers, Cathrine; Chowdhury, Sudipa; Wright, W Shea et al. (2017) Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses. AIDS 31:2199-2209
Lucas, Julie L; Tacheny, Erin A; Ferris, Allison et al. (2017) Development and validation of a Luminex assay for detection of a predictive biomarker for PROSTVAC-VF therapy. PLoS One 12:e0182739
Xia, Li; Schrump, David S; Gildersleeve, Jeffrey C (2016) Whole-Cell Cancer Vaccines Induce Large Antibody Responses to Carbohydrates and Glycoproteins. Cell Chem Biol 23:1515-1525
Muthana, Saddam M; Gildersleeve, Jeffrey C (2016) Factors Affecting Anti-Glycan IgG and IgM Repertoires in Human Serum. Sci Rep 6:19509
Xia, Li; Gildersleeve, Jeffrey C (2015) The Glycan Array Platform as a Tool to Identify Carbohydrate Antigens. Methods Mol Biol 1331:27-40
Muthana, Saddam M; Gulley, James L; Hodge, James W et al. (2015) ABO blood type correlates with survival on prostate cancer vaccine therapy. Oncotarget 6:32244-56
Yin, Zhaojun; Chowdhury, Sudipa; McKay, Craig et al. (2015) Significant Impact of Immunogen Design on the Diversity of Antibodies Generated by Carbohydrate-Based Anticancer Vaccine. ACS Chem Biol 10:2364-72
Muthana, Saddam M; Xia, Li; Campbell, Christopher T et al. (2015) Competition between serum IgG, IgM, and IgA anti-glycan antibodies. PLoS One 10:e0119298
Campbell, Christopher T; Gulley, James L; Oyelaran, Oyindasola et al. (2014) Humoral response to a viral glycan correlates with survival on PROSTVAC-VF. Proc Natl Acad Sci U S A 111:E1749-58
Muthana, Saddam M; Gildersleeve, Jeffrey C (2014) Glycan microarrays: powerful tools for biomarker discovery. Cancer Biomark 14:29-41

Showing the most recent 10 out of 19 publications