Sequence enrichment profiles enable target-agnostic antibody generation for a broad range of antigens

ExpoSeq: simplified analysis of high-throughput sequencing data from antibody discovery campaigns

“…One of the most commonly used in vitro display methods is antibody phage display technology, which involves biopanning of an antibody-displaying phage library against a target, upon which typically only a relatively small subset of the selected binders are picked for screening, (Sanger) sequencing, and functional assays ( Ledsgaard et al 2018 , Alfaleh et al 2020 ). While antibody phage display technology has been utilized to discover several successful therapeutic antibodies, such as one of the top-selling drugs, adalimumab ( Ecker et al 2015 , Grilo and Mantalaris 2019 ), recent studies suggest that to truly unlock the full potential of display technologies, high-throughput sequencing (HTS) is key ( Domina et al 2014 , Liu et al 2015 , Yang et al 2017 , Ljungars et al 2019 , Mattsson et al 2023 ). The reason for this is that HTS allows for the screening and analysis of the entire pool of antibodies during the biopanning process, rather than the assessment and characterization of only a small subset of the most abundant clones.…”

Two-dimensional high-throughput on-cell screening of immunoglobulins against broad antigen repertoires

“…Despite the promise of using scRNA-seq to identify Ag-specific Abs, the limitation in the number of analyzed cells (up to 20000 per assay), high cost per sample, and the necessity to obtain recombinant antigens in the first instance, complicates the identification of rare therapeutic Ag-specific Abs with an a priori unknown specificity. Alternatively, therapeutic antibodies against most new disease-associated biomolecules can be obtained via phenotypic drug discovery approach 12 . This cell-based phenotypic screening theoretically enables identifying novel drugs without understanding a complex mechanism of pathogenesis.…”