CD28 and acute lymphoblastic leukemia: Indeed, in keeping with observations in animal studies (12), T cells engineered with a CD19-specific second-generation CD28/CD3ζ dual-signaling CAR (CD19-28z) displayed superior in vivo persistence than first-generation ones, and resulted in favorable clinical responses in ALL and in patients with advanced B-cell Non-Hodgkin lymphomas (B-NHL) (18, 19).