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Abstract Cancer immunotherapy with autologous chimeric antigen receptor (CAR) T cells faces challenges in manufacturing and patient selection that could be avoided by using ‘off-the-shelf’ products, such as allogeneic CAR natural killer T (^AlloCAR-NKT) cells. Previously, we reported a system for differentiating human hematopoietic stem and progenitor cells into^AlloCAR-NKT cells, but the use of three-dimensional culture and xenogeneic feeders precluded its clinical application. Here we describe a clinically guided method to differentiate and expand IL-15-enhanced^AlloCAR-NKT cells with high yield and purity. We generated^AlloCAR-NKT cells targeting seven cancers and, in a multiple myeloma model, demonstrated their antitumor efficacy, expansion and persistence. The cells also selectively depleted immunosuppressive cells in the tumor microenviroment and antagonized tumor immune evasion via triple targeting of CAR, TCR and NK receptors. They exhibited a stable hypoimmunogenic phenotype associated with epigenetic and signaling regulation and did not induce detectable graft versus host disease or cytokine release syndrome. These properties of^AlloCAR-NKT cells support their potential for clinical translation. 

The oxygen reduction reaction (ORR) on platinum catalysts is essential in fuel cells. Quantitative predictions of the relative ORR activity in experiments, in the range of 1 to 50 times, have remained challenging because of incomplete mechanistic understanding and lack of computational tools to account for the associated small differences in activation energies (<2.3 kilocalories per mole). Using highly accurate molecular dynamics (MD) simulation with the Interface force field (0.1 kilocalories per mole), we elucidated the mechanism of adsorption of molecular oxygen on regular and irregular platinum surfaces and nanostructures, followed by local density functional theory (DFT) calculations. The relative ORR activity is determined by oxygen access to platinum surfaces, which greatly depends on specific water adlayers, while electron transfer occurs at a similar slow rate. The MD methods facilitate quantitative predictions of relative ORR activities of any platinum nanostructures, are applicable to other catalysts, and enable effective MD/DFT approaches.