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Targeting Transmembrane Proteins: Facilitating Rapid Advancement in Therapeutic Antibody Discovery

Abstract Transmembrane proteins usually play pivotal roles in various cellular processes, including signal transduction, cell adhesion, and molecular transport, and have emerged as key targets for therapeutic antibody discovery. These integral membrane proteins are closely related to numerous diseases, such as cancer, autoimmune diseases, and infectious diseases. By specifically binding to these transmembrane proteins, therapeutic antibodies can modulate their function, block interactions with ligands, or induce targeted immune responses. However, due to the unique characteristics and location of transmembrane proteins within the lipid bilayer of cell membranes, it is challenging for them to become successful drug targets. These proteins often have complex topologies with both hydrophobic and hydrophilic regions, making it difficult for antibodies to access and bind to their functional domains with high specificity and affinity. Full-length transmembrane proteins have recently seen increased prospects for successful drug development strategies, as they maintain unique epitopes on the extracellular regions of the protein and have enhanced our ability to predict and validate druggable sites on transmembrane proteins. Through this talk, we aim to discuss technical platforms for expression of full-length transmembrane proteins and show available technical platforms from CUSABIO and how CUSABIO facilitate rapid advancement in therapeutic antibody discovery based on these platforms, as well as successful cases from CUSABIO. Key Content 1. Transmembrane proteins hold a central role in drug targets 2. An introduction to principal technical platforms for expressing transmembrane proteins 3. Successful expression of multi-pass transmembrane proteins facilitates therapeutic antibody discovery and case sharing