Featuring presentations from Retrogenix, Novartis and BMS / Juno, this webinar covers assessing off-target liabilities and generating tox data for INDs.
The adverse effects of off-target mediated CAR T activation in healthy tissues could be catastrophic for patients who receive novel cell therapies. As such, ensuring that cell therapies are specific to their intended targets is vital, particularly when assessing potential safety implications prior to clinical studies.
Target-related safety risks for chimeric antigen receptor (CAR) T cell therapies occur either through unanticipated on-target/off tumour binding, or via lack of specificity of the CAR targeting element which results in off-target mediated activation. Specificity to the primary target can be assessed by screening for binding against thousands of human proteins that are individually over-expressed…
Ensuring that a novel biotherapeutic is specific to its intended target is undoubtedly advantageous when selecting promising lead candidates, however, it becomes vital when assessing potential safety implications prior to clinical studies.
This webinar provides an overview of the Cell Microarray technology, with a particular focus on specificity/off-target screening, featuring presentations by GSK, UltraHuman and Retrogenix.
Retrogenix expresses thousands of full-length human proteins in the context of human cells in order to detect relevant interactions with test molecules.
The animation on this website provides an overview of how we set up the cell microarrays and use the technology to identify primary receptors targets and off-targets for a wide variety of ligands.
Ligand-receptor interactions that are dependent on proper expression, post-translational modification and correct folding of a complete heterodimeric unit, can now be detected using cell microarray screening. This poster describes the evolution of the platform to include co-expressed heterodimers, using CD3 & integrin family interactions to demonstrate the expanded power of the library for screening key cell surface receptors.
As secreted proteins are not naturally localised on the cell surface, novel constructs which result in expression of ‘secreted’ proteins that are tethered to the plasma membrane have been developed and tested. Extensive validation work confirmed proof of principle and led to the development of the ‘high confidence’ library of secreted proteins now included in cell microarray screening….
This poster presents data from two off-target screens showing how the Retrogenix approach rapidly identifies specific and relevant off-targets with a very low rate of false positive results. The first study demonstrates target specificity and the second uncovers a previously unidentified, critical off-target…
Download our SOT 2017 poster describing the how the Retrogenix human cell microarray technology has been optimised to screen whole CAR T cells for specific interactions, reducing the risk of unanticipated off-target adverse effects in the development of novel immunotherapies and providing essential supporting data for pre-IND safety assessment.
Download a recent poster presented at PEGS Boston to see some typical results from a cell microarray screen and learn how the Retrogenix technology can assist with immune checkpoint pairing.
Further examples of the applications of the cell microarray technology can also be found in the case studies resource on this website.
Biologics such as antibodies are widely favoured in drug discovery due to their inherent potential for specificity to a single target antigen. Despite this, off-target mediated toxicity could present an issue for a subset of antibodies and other molecules in development. Download our PEGS 2017 poster to learn how the Retrogenix human cell microarray technology approach is being applied to identify specific and relevant off-targets with a very low rate of false positive results.