Conference dates: May 13-17, 2024

Booth: 301

Location: Omni Boston Hotel at the Seaport, Boston MA

Poster session

Poster 1 Title: Large-Scale Characterization of Drug Candidates Against Transmembrane Receptors Using HT-SPR

Presenter: Maria McGresham, PhD, Field Applications Scientist, Carterra

Poster Number: A025

Abstract: Membrane targets make up a substantial part of the overall “undruggable” therapeutic space that has recently garnered widespread interest. Despite encouraging improvements in the tools to screen for therapeutics against membrane-bound targets, there are still many practical limitations owing to the challenges of working with proteins that are not highly stable outside of the cellmembrane environment. High-throughput surface plasmon resonance (HT-SPR) is a powerful technique that is transforming characterization workflows and enabling a greater breadth and depth of information for drug candidates. Here we demonstrate the ability to quantitatively assess binding kinetics for panels of antibodies against membrane receptors in several formats. This workflow highlights opportunities to perform detailed binding characterization for up to thousands of drug candidates in parallel.


Poster 2 Title: HT-SPR Evaluation of Fc Gamma Receptor Binding using Carterra LSAXT

Presenter: Maria McGresham, PhD, Field Applications Scientist, Carterra

Poster Number: B020

Abstract: Fc gamma receptors (FcγRs) are a family of proteins expressed on the surface of immune cells that can elicit activating or inhibitory responses when bound by the Fc domain of IgG antibodies. IgG Fc-containing biologics are a substantial and growing class of drugs with over 175+ antibody therapeutics already approved or undergoing regulatory review (The Antibody Society, 2023). These biologics include IgG-based mAbs, multispecific antibodies, and Fc-fusion proteins. The Fc domain can be mutated to improve, diminish, or abrogate FcγR binding. It can also be mutated to heterodimerize Fc chains for multispecific antibody construction or to extend FcRn mediated half-life, to name a few common mutational strategies. In each application, assessing the mutational impact on each FcγR interaction relative to the wild-type Fc is critical as they are all bound by a common site in the hinge region of the Fc domain and can impart different FcγR-mediated immune responses as a function of their affinity. It is also critical to assess the binding of wild-type and engineered Fc domains to relevant species FcγRs if the therapeutic is intended to be administered to the respective species for proper drug characterization and data interpretation across species. FcγR affinities are commonly measured using lower throughput, high sensitivity biosensing instruments to accurately characterize these interactions and require significant lab time, instrument usage, and protein. Pairing Carterra’s LSAXT with ACROBiosystems’ proteins enables the development of a high-throughput assessment of FcγRs to simplify the characterization of IgG-Fc containing biologics. Herein, we detail a workflow utilizing High-Throughput SPR (HT-SPR) on the LSAXT to characterize trastuzumab (IgG1 mAb) against 11 FcγRs with high sensitivity and reproducibility in a fraction of the time and resources.