Jeff C. Gildersleeve: Understanding and Exploiting Anti-Glycan Immunity to Improve Cancer Care
Jeffrey C. Gildersleeve, Ph.D.
National Cancer Institute (NCI), Center for Cancer Research, USA
Cancer vaccines and other immunotherapies are producing substantial clinical benefits to cancer patients, but clinical responses vary considerably from patient to patient. To optimize their clinical use, there are major efforts to (a) identify predictive biomarkers (markers that could be used to select patients that are likely to have a positive response), (b) identify biomarkers of efficacy (markers that could be used to determine if a patient is having a favorable response), and (c) develop better vaccines/immunotherapies. A key to achieving these goals is developing a better understanding of what constitutes a favorably immune response. While responses to proteins have been studied at length, immune responses to glycans have been largely understudied. Carbohydrate microarrays provide a convenient, high-throughput tool for profiling anti-glycan antibody populations in serum and identifying unique or altered subpopulations that are relevant to clinical outcomes. We have used this technology to evaluate immune responses induced by a poxvirus-based prostate cancer vaccine (PROSTVAC-V/F) that is currently in Phase III clinical trials. We have profiled over 140 patients from two Phase II clinical trials and have identified serum antibodies with statistically significant correlations with overall survival. These antibodies are promising new biomarkers for predicting which patients will respond favorably to PROSTVAC-VF and are being developed as companion assays for PROSTVAC-VF. We have also used the glycan microarray to evaluate antibody responses to GVAX Pancreas, a whole cell vaccine in Phase II clinical trials. Our results provide new insights for improving vaccine design.