In this webinar, Clayton Kosonocky and Wesley A. Wierson examine how large-scale CAR T-cell functional validation informs the efficacy of AI-driven protein binder design methodologies. They present Bits to Binders, a global competition where teams from 42 countries used diverse in silico protein design pipelines to engineer and submit 12,000 de novo antigen binders. Rather than simply testing binding, this competition aimed to directly validate in silico binders as functional CAR T cells in a primary human T cell screen, and team hit rates ranged from 0.6 to 38.4 percent. They validated the top-performing candidates as individual constructs across other T cell functional assays including proliferation, cytokine production, and tumor killing, and found that several designs were broadly functional. From this data, common design methodologies and factors correlated with DNA synthesis, expression, and target-specific T cell activation were identified, which nearly double the success rates when applied as a retrospective filter. They release the full dataset as an open resource, with practical recommendations to support more effective AI-driven binder design.