Bispecific antibodies are promising therapeutics for targeting cancer cells with high specificity. The measurement of binding rates and avidity effects in the simultaneous engagement of two antigens by a bispecific antibody is key for understanding
and optimizing target selectivity early in the drug development process. The quantitative analysis of individual and cooperative target binding, as well as target selectivity, provides insight on how to engineer the individual affinities of
the bispecific antibody arms to achieve minimal off-target binding.
We will describe the application of a novel type of biosensor that uses DNA-guided surface functionalization for the precise control over the relative abundance and spatial arrangement of two antigen species. The biosensor emulates the display
of two different target antigens on a cancer cell surface and enables dual-color fluorescence detection for the simultaneous single and dual-binding kinetic studies of bispecific antibodies.
We will illustrate how different assays can be set up to generate key read-outs for different applications. Biosensor real-time recording capabilities enable the experimenter to determine kinetic parameters (on and off rates) and thermodynamic
parameters (equilibrium constants) of both individual and cooperative binding. We will show you how to interrogate the contribution of both binding sites to the overall bispecific construct kinetic behavior, ultimately determining surface
residence times of a bispecific antibody on sensor surfaces that simulate different cancer cell lines.
- Measure kinetic parameters: how to analyze affinity and avidity binding of bispecific antibody constructs
- Assay setup: how to use target ratio and density control to modulate target engagement
- Analysis: what is the contribution of each binding site and how this translates to read-outs such as surface half-life
- Practical implications: how to measure cooperative binding and predict target selectivity
Joanna Deek, PhD
Senior Scientist, Science Department
Dynamic Biosensors, Inc.
Joanna Deek is Head of Business Development for the US market at Dynamic Biosensors. In her scientific role at DBS, she established switchSENSE® assays to qualify target selectivity of bispecific antibody constructs, using affinity modulated
anti-EGFR and anti-Her2 antibodies. Pior to joining DBS, she did a postdoc at the Technical University of Munich, at the Chair of Biophysics, where she investigated the impact of disease-associated phosphorylation on the phenotypes of soft
epithelial human keratin proteins. She obtained her PhD from the Department of Chemistry and Biochemistry at the University of California, Santa Barbara, where she investigated the structure-function relationship of neurofilament hydrogels.
Dr. Stefanie Mak
Application Specialist, Science Department
Dynamic Biosensors GmbH
Stefanie Mak is an Application Specialist at Dynamic Biosensors. She obtained her PhD in Clinical Chemistry at the Technical University of Munich, Germany, working on a novel biosensor principle for the detection of autoreactive antibodies in
patient serum. After changing to DBS, she became part of the Cell & Antibody team, specializing in bispecific antibodies. She established new assay setups and analytical approaches, most notably using Y structure DNA for the analysis of
weak binders such as the therapeutic antibody Hemlibra.
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