Abstract 1247: Screening the membrane proteome to determine antibody specificity and discover new immunomodulatory targets

Abstract

Abstract The Membrane Proteome Array (MPA) is a cell-based expression array of more than 5,300 membrane proteins that enables the screening of preclinical antibodies for off-target binding and the deorphaning of phenotypic antibodies to identify their associated targets. Each membrane protein is expressed in live cells in its native conformation with appropriate post-translational modifications. Binding interactions are tested and validated using high-throughput flow cytometry, providing a comprehensive assessment of antibody binding across the membrane proteome. Membrane proteins in the MPA are fully functional and can be used for phenotypic screening to identify new therapeutic targets. Using a T-cell co-culture approach, we identified dozens of novel co-stimulatory proteins, as well as many well-validated proteins known to be involved in T-cell activation. The proteins identified in this screen represent novel therapeutic targets across multiple membrane protein classes and likely function on diverse axes of T-cell regulation. Citation Format: Duncan Huston-Paterson. Screening the membrane proteome to determine antibody specificity and discover new immunomodulatory targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1247.