Leading up to the Antibody Engineering Event, we'll be sharing the posters that will be featured in the Exhibit Hall. Antibody Engineering & Therapeutics will take place December 8-12, 2013 in Huntington Beach, California. For more information the program, download the agenda. If you'd like to join us, as a reader of this blog, when you register to join us and mention code XD13172BLOGJP, you'll save 20% off the standard rate!Featured Poster: Removal of a C-terminal serine residue proximal to the inter-chain disulfide bond of a human IgG1 lambda light chain mediates enhanced antibody stability and antibody dependent cell cytotoxicity (ADCC)
Featured Presenter: Yang Shen, ImClone Systems
About the Poster: Optimization of biophysical properties is a critical success factor for the developability of monoclonal antibodies with potential therapeutic applications. The inter-domain disulfide bond between light chain (Lc) and heavy chain (Hc) in human IgG1 lends structural support for antibody scaffold stability, optimal antigen binding, and normal Fc function. Recently, human IgG1l has been suggested to exhibit significantly greater susceptibility to reduction of the inter Lc-Hc disulfide bond relative to the same disulfide bond in human IgG1k. To understand the molecular basis for this observed difference in stability, the sequence and structure of human IgG1l and human IgG1k were compared. Based on this Lc comparison, three single mutations were made in the λ Lc proximal to the cysteine residue, which forms a disulfide bond with the Hc. We determined that deletion of S214 (dS) improved resistance of the association between Lc and Hc to thermal stress. In addition, deletion of this terminal serine from the Lc of IgG1l provided further benefit, including an increase in stability at elevated pH, increased yield from transient transfection, and improved in vitro antibody dependent cell-mediated cytotoxicity (ADCC). These observations support that the presence of the terminal serine of the l Lc creates a weaker inter-chain disulfide bond between the Lc and Hc, leading to slightly reduced stability and a potential compromise in IgG1l function. Our data from a human IgG1l provides a basis for further investigation of the impact by deleting terminal serine from lLc on the stability and function of other human IgG1l antibodies.
Do you have new research to share with your industry colleagues? Your poster can be featured in the Antibody Engineering Exhibit hall as well! Find out how here. The deadline for poster submissions is November 1.
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