Innovations and trends in antibody repertoire analysis

Abstract

Monoclonal antibodies have revolutionized the treatment of human diseases, which has made them the fastest-growing class of therapeutics, with global sales expected to reach $346.6 billion USD by 2028. Advances in antibody engineering and development have led to the creation of increasingly sophisticated antibody-based therapeutics (e.g. bispecific antibodies and chimeric antigen receptor T cells). However, approaches for antibody discovery have remained comparatively grounded in conventional yet reliable in vitro assays. Breakthrough developments in high-throughput single B-cell sequencing and immunoglobulin proteomic serology, however, have enabled the identification of high-affinity antibodies directly from endogenous B cells or circulating immunoglobulin produced in vivo. Moreover, advances in artificial intelligence offer vast potential for antibody discovery and design with large-scale repertoire datasets positioned as the optimal source of training data for such applications. We highlight advances and recent trends in how these technologies are being applied to antibody repertoire analysis.