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High-throughput kinetic profiling of monoclonal antibodies
The development of monoclonal antibodies (mAbs) e.g. as lead candidates for new biologics starts with the creation of a large screening pool of individual cell cultures in microplates. After a primary screening typically performed by ELISA tests towards the presence of active antibodies it is necessary to select the best lead candidates for the laborious and expensive next level in the development chain. The usual label-free technique used nowadays demonstrated some limitations in throughput, too low estimated affinity or a liability in identifying kd correctly.
To this end, bscreen offers a novel workflow for secondary screening of monoclonal antibodies which combines an unsurpassed high-throughput with high quality kinetic data.
Kinetic characterisation of monoclonal antibodies from cell culture supernatants
Finding high-affinity antibody candidates is an important goal in the early stages of monoclonal antibody (mAb) development. The biggest challenge for analysing antibodies in the early discovery stage is the complexity of the samples. Depending on their expression system, antibodies are produced in different media and in a wide range of concentrations. In addition, influences of medium components, like serum, need to be considered for precise and reliable analytics. We demonstrated how to overcome these challenges with bscreen. bscreen combines microarray technology with kinetics, offering richer data sets that improve hit identification and provide better lead candidates for characterisation, accelerating the pipeline for new drug discoveries. We established an easy to follow workflow to optimise the immobilisation procedure for mAbs directly from cell culture supernatants for subsequent label-free screening and affinity ranking on the bscreen system. bscreen can easily be employed to screen up to 9000 mAbs per day and rank them according to their affinity, enabling the screening of an entire library in days as opposed to weeks.Download PDF
HTS epitope mapping for antibody characterisation.
Therapeutic antibodies represent a relatively new group among the pharmaceutically interesting substances. But as all substances they need to be carefully characterised. We show the possibility for HTS epitope mapping on the bscreen platform on the example of a well, characterised antibody system.Download PDF
Identification of (cancer) biomarkers and potential new drugs via HTS screening of protein-peptide interactions.
Peptides can serve as pharmacological active substances if synthesised accordingly. Usually a large pool of peptides has to be screened and the selected hits have to be tuned in terms of sequence to optimise the affinity of the peptides to their target. We show the possibility to select and characterise different peptides interacting with the Grb2 protein, which plays a crucial role in cancer. bscreen anables the screening of high-density peptide arrays in a fast and reliable workflow.Download PDF
Discrimination between agonistic and antagonistic behaviour of pharmaceutical relevant substances.
Classical assay design only allows to discriminate between binding or non-binding of pharmaceutically relevant substances to their targets. Although it might be possible to discriminate between agonistic and antagonistic behaviour via enthalpy and entropy, this is not done easily and sometimes simply impossible. We present an alternative way how this can be achieved much easier via an intelligent assay design on the example of the Estrogen Receptor alpha and two model substances.
Investigation of receptor / small molecule interaction.
The interaction of the Estrogen Receptor alpha and a pharmaceutically active substance was monitored and the biomolecular interaction was characterised. Kinetic rate constants as well as the affinity of the small molecule towards the receptor was obtained.