title: A fully automated primary screening system for the discovery of therapeutic antibodies directly from B cells.
abstract: For a therapeutic antibody to succeed, it must meet a range of potency, stability, and specificity criteria. Many of these characteristics are conferred by the amino acid sequence of the heavy and light chain variable regions and, for this reason, can be screened for during antibody selection. However, it is important to consider that antibodies satisfying all these criteria may be of low frequency in an immunized animal; for this reason, it is essential to have a mechanism that allows for efficient sampling of the immune repertoire. UCB's core antibody discovery platform combines high-throughput B cell culture screening and the identification and isolation of single, antigen-specific IgG-secreting B cells through a proprietary technique called the "fluorescent foci" method. Using state-of-the-art automation to facilitate primary screening, extremely efficient interrogation of the natural antibody repertoire is made possible; more than 1 billion immune B cells can now be screened to provide a useful starting point from which to identify the rare therapeutic antibody. This article will describe the design, construction, and commissioning of a bespoke automated screening platform and two examples of how it was used to screen for antibodies against two targets.
authors.affiliation: UCB Pharma, Slough, UK simon.tickle@ucb.com.
authors.forename: Simon
authors.initials: S
authors.lastname: Tickle
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Howells
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: O'Dowd
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: Dale
authors.initials: D
authors.lastname: Starkie
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Whale
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Saunders
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: David
authors.initials: D
authors.lastname: Lee
authors.affiliation: UCB Pharma, Slough, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lightwood
mesh_terms: D000818:Animals; D000906:Antibodies / Q000302:isolation & purification / Q000627:therapeutic use*; D001331:Automation; D001402:B-Lymphocytes / Q000276:immunology*; D011817:Rabbits; D051381:Rats
chemical_list: D000906:Antibodies
keywords: antibody; automation or robotics; database and data management; large molecule therapeutics; liquid handling