Tu198 - Association of Treatment Outcomes with Fc-dependent Antibody Effector Functions Using Systems Serology

Amanda Gross – SeromYx Systems; Thomas Broge – SeromYx Systems; Thomas Linnekin – SeromYx Systems; William Graham – SeromYx Systems; Kimberly Piper – SeromYx Systems; Henry Buda – SeromYx Systems; Lev Brown – SeromYx Systems; Tom Shneer – SeromYx Systems; Jishnu Das – Department of Immunology; Department of Computational & Systems Biology – University of Pittsburgh

Abstract Text: Growing evidence for associations between humoral immune responses and development of cancer and autoimmunity suggests that antibodies may be useful biomarkers for prediction of disease progression and therapeutic efficacy. The fragment crystallizable (Fc) region in antibodies carries structural determinants of Fc receptor and complement component 1q binding that triggers effector innate immune cell and complement functions involved in homeostasis, pathogenesis, and therapeutic efficacy. A systems strategy that integrates the Fc-dependent biophysical and functional properties of diverse antibody repertoires and correlates corresponding multivariate profiles with specific outcomes or endotypes would be beneficial for biomarker identification. We have developed the Systems Serology platform that consists of a suite of robust, high-throughput, rapid, and highly reproducible bead- and plate-based assays, adaptable to analyze antigen-specific antibody responses. The platform has provided an unprecedented depth of resolution of qualitative differences in the humoral immune response to many bacterial, viral, fungal, and parasitic pathogens and has identified correlates of protection in vaccine trials. In a pilot cancer study, we investigated Fc-dependent effector functions in baseline and post-treatment serum samples from melanoma patients who received a novel toll-like receptor immunotherapy. Antibody effector functions such as antibody-dependent complement deposition and antibody-dependent NK cell activation were observed to be more robust earlier in treatment in the responder group compared to the non-responder group. The Systems Serology platform holds promise to uncover Fc-dependent effector functions associated with clinical outcome in areas of health concern beyond infectious disease.