Human cell microarray technology reduces risk of unanticipated off-target adverse effects
Manchester, UK and Cambridge, MA, 6th April 2017
Biotechnology company Retrogenix, the leader in identifying the specific human cell surface receptor targets for biological and pharmaceutical ligands, has enhanced its innovative cell microarray technology to enable specificity screening of whole chimeric antigen receptor (CAR) T cells. The advance helps address the urgent need for tools to assist with safety assessment of novel cancer immunotherapies.
CAR T cell therapy involves engineering a patient’s own immune cells to recognise and attack a specific tumour. As the therapy works by harnessing the immune system it is crucial to ensure that there are no unintended – or ‘off-target’ – interactions that could promote an inappropriate immune response with potentially fatal consequences. Using cells provided by a leading clinical stage T cell therapy company, Retrogenix has now developed an off-target profiling methodology which screens whole T cells for interactions against thousands of human plasma membrane protein targets. This advance builds on Retrogenix’s successes at screening the isolated functional elements (usually single chain variable fragments, or ‘scFvs’) that are ultimately engineered onto the T cells. CAR T cells are fluorescently labelled and screened for binding against over 4,500 human proteins that are individually over-expressed in distinct clusters of human cells on Retrogenix’s microarrays. This confirms binding of the CAR T cells to their primary target receptor and also ensures that there is no additional binding amongst this extensive panel of proteins that could indicate a potential off-target event. Commenting on the technology advance, Jo Soden, Executive Director of Retrogenix, said: “Understanding potential off-target liabilities is a key concern for all drug developers regardless of whether they are focused on small molecules, antibodies or cell-based therapies. Since this development we’ve been working with several other CAR T biotechs, all requiring evidence and reassurance that there is minimal risk of off-target events before their therapies progress through to patients.”
Dr Jim Freeth, Retrogenix’s Managing Director, added: “We are delighted to now deliver a novel and unique service that helps de-risk immunotherapy development and provides essential supporting data for pre-IND safety assessment.” The results of this technology optimisation project were presented at the 2017 Society of Toxicology (SOT) meeting which was held last month in Baltimore, MD.