High-throughput drug screen to identify drugs modulating CAR T-cell cytotoxicity. (A) Schematic of the high-throughput coculture system drug sensitivity screen. (B) NALM6-luc cell viability with different effector/target ratios of CAR T cells or empty vector–transduced control T cells and NALM6-luc cells cocultured for 24 hours. (C) Overview of drug responses in CAR T-cell cytotoxicity screen. A positive differential DSS between CAR T cell–treated and control screens indicates that the compound enhances CAR T-cell cytotoxicity, whereas a negative score indicates inhibition. (D) Top 20 drugs most potently inhibiting CAR T-cell cytotoxicity ordered by the differential DSS. (E) Top 15 drugs most potently enhancing CAR T-cell cytotoxicity ordered by the differential DSS. NSAID, nonsteroidal anti-inflammatory drug.