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337,234
2020-12-01 to 2022-05-31
Study
Antibody Analytics (AA) is a Contract Research Organisation dedicated to advancing drug development by providing primary cell methods and bioassays complemented by a wide range of binding capabilities to help progress customers' therapeutic candidates from early discovery and throughout clinical development. Bispecific antibody (BsAb)-based oncology therapeutics are promising therapeutic modalities, but their multi-specific nature introduces layers of complexity when trying to demonstrate efficacy and safety. There is a lack of appropriate _in vitro_ systems to assess the impact of the relative levels of cell-surface protein levels of the respective targets on efficacy and safety. This is vitally important for T cell engagers and CAR-T cells, which are hampered by 'on-target/off-tumour' toxicity towards healthy tissues (_J. Immunotoxicol._ **17**, 67--85). This side-effect is often not observed until the clinical trial stage, at which point significant financial investment has been made. Our innovation will address this by developing IndEx-2, a cell line platform in which the expression of multiple antigens can be independently controlled. Comprised of a 'landing pad' cell line (enabling rapid genome-directed integration) combined with novel inducible promoters, this will provide independent fine tuning of expression of two distinct antigens that can be quantified and correlated with antigen expression levels in healthy and tumour tissue. IndEx-2 will allow drug developers to rapidly and cost-effectively determine the precise antigen density activation thresholds of their candidates. Coupled with AA's immuno-oncology (I-O) assay services this will provide a complete picture of a candidate's mechanism of action (MoA) and safety profile. By enabling selection of candidates with improved efficacy and enhanced safety profiles at the discovery stage, the risk of failure at the expensive toxicology and clinical trial stages will be reduced.