Indeed, a clinical trial in which patients with refractory non-Hodgkin’s lymphoma (NHL) were simultaneously infused equal amounts of first generation CD-19 targeted CAR T cells, or second-generation CD-19 CAR T cells clearly demonstrated that costimulation improved the in vivo expansion and persistence of CAR-modified T cells when combined with the costimulatory CD28 domain (69). This evidence concerns the gene CD28 and non-Hodgkin lymphoma.