Unlocking Challenging Targets: Deep Screening of Natural Immune Repertoires at the Single-Cell Level for Therapeutic Antibody Discovery

摘要

AbCellera has developed a radically advanced end-to-end antibody discovery platform that enables direct selection of high-value antibodies from single B cells from any species, for any target, and with a throughput of millions of cells per day. Antibody-secreting cells (ASCs) from patients or immunized animals are loaded into microfluidic devices containing large arrays of nanoliter-volume cell analysis chambers. Compartmentalization of ASCs in smallvolume chambers that are configured to allow exchange of reagents enables a wide array of miniaturized selection assays. These include bead-based binding measurements for affinity, specificity and competition, in addition to customizable cell-based assays for binding or functional selections. We will demonstrate the power of this technology using three different examples. First, we will present data for discovery of rodent antibodies against a target with 100% rat-human homology. We will demonstrate that ultra-deep screening of multiple immune tissues generates large and diverse panels of lead candidates. Second, we will demonstrate selection of antibodies from rats using direct cell binding assays to find ultra-rare cross-reactive antibodies against a membrane target with high rat-human homology. Finally, we will present how cellbinding assays can be used to generate highly diverse panels of antibodies against complex membrane proteins, including ion channels. AbCellera’s technology overcomes limitations of immune tolerance, provides ultra-deep throughput, and offers a suite of complex selection assays to deeply screen and access the full potential of natural immune repertoires, generating hundreds of lead candidates, and moving from cell isolation to sequences and recombinant antibodies in as little as 4 weeks.