New Assays and Tools for the Development of Antibody Biotherapeutics. See the full agenda here.
Cellular Dynamics Presentation
Predicting Cardiac Risk of Anti-cancer Therapies in iPSC-derived Cardiomyocytes: from Small Molecules to Biologics.
Giorgia Salvagiotto, PhD – Cellular Dynamics International, a FUJIFILM company
Abstract: Human cell types differentiated from induced pluripotent stem cells (iPSCs) offer an attractive source of cellular material for both basic research and drug discovery because of the biologically relevant systems they can represent in vitro. The iPSC technology is a key element for modeling human biology in a dish, which is otherwise difficult to explore using conventional cell lines, primary cells, or animal models. Our approach is to generate iPSC-derived cell types with high quality, purity, and unlimited quantities, design relevant assays with cells derived from apparently healthy donors, and develop disease models using environmental stimuli or disease-specific, patient-derived cells.
Cardiotoxicity is a major complication of different classes of anti-neoplastic therapies. Current strategies for detecting cardiotoxicity risks are minimal and often ineffective, mainly due to the limitations of current in vitro models. The talk will present iPSC-derived cardiomyocytes, their characterization, and their functional utility to detect cardiac liabilities. In particular, we will discuss the following studies: validation of cell-based assays to detect cardiotoxicity using luminescence, impedance-based, or multi-electrode array systems; description of an impedance-based assay to predict small molecule kinase inhibitor-related toxicities; identification of early biomarkers relevant for the management of cardiotoxicity from monoclonal antibody therapies for HER2+ breast cancer; retrospective analysis of off-tumor cardiac toxicity occurred in clinical phase with high affinity engineered TCR-based immunotherapy.
In summary the presentation will show how iPSC-derived cardiomyocytes could potentially be included in early detection of cardiac liability across different therapeutic classes, given the advantage of the iPSC technology in providing access to biologically relevant human models opening new opportunities to address the limitations of primary cells and immortalized cell lines.