Besides preclinical studies, a clinical trial in 16 patients with r/r non-Hodgkin’s lymphoma showed that the third-generation anti-CD19 CAR T-cells (CD28 and 41-BB) exhibited stonger anti-tumor activity than the second-generation CAR T-cells (CD28 only) with mild cytokine release syndrome (CRS) in 6 patients20. This evidence concerns the gene CD28 and non-Hodgkin lymphoma.