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Immune checkpoint receptors play critical roles in maintaining immune homeostasis and are critically associated with autoimmune disease,cancer and persistent viral infections.Antibodies targeting immune checkpoints have emerged as promising approach to enhance anti-tumor immune responses.A significant challenge in the development of biologics that target immune checkpoints is access to quantitative and reproducible potency bioassays when traditional methods rely on primary cells and lengthy and tedious measurement of cytokine production.Here,I will present the latest advancement on novel reporter gene potency bioassay development and demonstrate how they can be used for a broad range of applications including QC lot release during drug development for single and combination immunotherapy.In the case studies,I will present data on immune checkpoint bioassays for monoclonal antibody targeting single receptor(PD-1,CTLA-4,LAG-3,4-1 BB,ICOS),and several combination bioassays designed for bispecific antibodies targeting PD-1 and a second immune checkpoint receptor.