Bispecific Antibodies (BsAbs)
Bispecific antibodies (BsAbs) are innovative class of therapeutic proteins designed with two binding sites directed at either two different antigens or two different epitopes on the same antigen simultaneously. A growing number of BsAbs are being explored for applications in cancer treatment and beyond for non-oncology indications like autoimmune diseases, infectious diseases, and other conditions.
Compared to traditional monoclonal antibodies, BsAbs offer enhanced cytotoxic effects due to dual targeting and broader applications for several indications.
FDA approved and clinical pipeline candidate BsAbs are available in different formats and mediate their therapeutic function via different molecular mechanisms.
Common bsAb formats include single-chain variable fragment (scFv) based BsAbs, tandem scFvs, CrossMab, DARTs (Dual-Affinity Re-Targeting Antibodies) and Triomabs, which are trifunctional antibodies that can bind to two different antigens and engage T-cells. The bispecific T cell engager (BiTE) antibodies connect two scFvs that bind to a cancer cell and a T-cell.
Thorough characterization of BsAbs is challenging due to their diverse formats to ensure their safety and efficacy. This includes detailed analysis of their pharmacokinetics, pharmacodynamics, immunogenicity, and potential toxicities.
Sartorius addresses these challenges with advanced analytical techniques to ensure that BsAbs are developed with the desired quality and specificity.
Bispecific Antibody R&D Workflow
Featured Products for Bispecific Antibodies (BsAbs) R&D
Octet® Label-Free Protein Analysis Platforms
Octet®️ platforms, available using Biolayer Interferometry (BLI) and Surface Plasmon Resonance (SPR), measure protein-protein interactions in parallel, without the use of detection agents.
Minimize time, effort, and costs in the assay development of bispecific therapeutics with the high-throughput Octet® RH96 system:
- Real-time BsAb binding assay to both antigens and titer determination
- Characterization of affinity and binding kinetics
- Rapid screening of cell lines and identification of pools and clones with higher concentrations of bispecific antibodies
Explore Label-Free Protein Analysis Read Case Studies
iQue® High-Throughput Screening (HTS) Cytometry Platform
The iQue® HTS Cytometry Platform is a high-throughput, suspension cell and bead analysis platform for multi-attribute screening of different antibody formats. It is the platform of choice for cell phenotype and function analysis in a single well and provides features that help streamline workflows and shorten time-to-results. The iQue® 21 CFR Part 11 Software Module ensures easy transitions from research lab towards regulated laboratories.
Evaluate mechanism of actions of different types of bispecific antibodies, i.e. CD3xCD19 Bispecific T Cell Engager (BiTE) Antibodies and identify temporal changes in the tumor microenvironment.
- Antibody internalization
- Antibody-Mediated T Cell Activation
- Analysis of T Cellular Subset, Activation Markers
- Cytokine Profiling
- Evaluation of Target Cytotoxicity
Incucyte® Live-Cell Analysis System
The Incucyte® Live-Cell Analysis System is designed to efficiently capture cellular changes where they happen - in the incubator. It enables in-depth functional and phenotypic assessment of several cell types and cellular interactions such us immune cell activation, cell health and proliferation.
Incucyte® 21 CFR Part 11 Software Module offers comprehensive security and electronic record keeping functionality.
- Morphological and Spatial Analysis of Immune and Tumor Cells
- Immune cell induced cytotoxicity - Immune Cell Killing
- Quantification of Target and Effector Cell Numbers
- Cell proliferation, health, apoptosis,
- Antibody Internalization
CellCelector Fully Automated Cell Selection and Retrieval Platform
The CellCelector Flex Platform is a fully automated cell imaging and picking system developed for screening, selection, and isolation of single cells, clones, clusters, and adherent colonies. It can process thousands of cells in parallel to identify and select optimal clones.
During Molecule and Cell Line Development, The CellCelector Flex can be used to:
- Isolate and clone specific cell lines that produce BsAbs
- Ensure monoclonality with extensive reporting capabilities
- Select and pick any CHO clones producing BsAbs
- Culture clones in a fraction of the space using Nanowell array technology
Picus® 2 Electronic Pipettes
Picus® 2 pipettes ensure reliable, repeatable pipetting results and feature an unbeatable ergonomic design that is kind to your hand.
- Connectivity
- Reproducible Results
- Guided Workflows
Sartorius Bispecific Antibodies (BsAbs) Solutions Offer:
The developed BLI method for BsAb binding and ProA titer measurement offers an easy screening method and workflow that assesses BsAb interactions in a versatile, label-free, and easy-to-use format.
Combining Incucyte® and iQue® analysis in a single assay plate enables more informed experimental design, mechanistic insights, and rapid progress to actionable results. Compatibility of the iQue® and Incucyte® workflows was demonstrated using a model of immune cell killing. Once maximal killing had been observed with Incucyte Live-Cell Analysis, cells were dissociated and evaluated using the iQue® T-Cell Activation kit antibody panel for identification of T cell subsets.
Miniaturized volume requirements for the iQue® platform enable repeated non-perturbing supernatant sampling. Study results demonstrated by using a modified miniaturized iQue® assay protocol, it was feasible to use only 20% of samples and assay reagents, thereby reducing sample consumption and reagent cost while maintaining assay sensitivity, quality, and reproducibility.
Frequently Asked Quesetions
Traditional technologies for characterizing antibodies, such as Enzyme-Linked Immunosorbent Assay (ELISA) and Surface Plasmon Resonance (SPR), have several limitations. They are often time-consuming and limited in their ability to provide quantitative functional assessment of two interactions to one bispecific molecule. This makes it challenging to evaluate complex bispecific therapeutics. Furthermore, these methods may not be suitable for high-throughput applications, which are often required in bioprocessing or cell line screening.
The Octet® Biolayer Interferometry (BLI) platform addresses these limitations by providing quantitative functional assessment of two interactions to one bispecific molecule in high-throughput applications.
These platforms and reagents together provide a comprehensive analysis of immune cell activation and tumor cell death. They allow for the study of multiple aspects of immune cell-tumor cell interactions, including morphological changes, cell numbers, and cytokine release. The real-time data analysis capability of the Incucyte® platform enables educated selection of time points for flow cytometric determinations on the iQue® platform This leads to more informed experimental design and efficient use of resources.
Incucyte® Live-Cell Analysis Immune Cell Killing assay offers morphological insights of immune cell activation and tumor cell death. Determination of the target cell number provides an indication of the degree of cytotoxicity elicited by the immune cells.
