As early as in 2014, several CAR T cell products targeting CD19 received U.S. FDA “breakthrough designation” like Memorial Sloan Kettering Cancer Center CD28-ζ CAR for adult B-ALL,112–114 University of Pennsylvania 4-1BB-ζ CAR for pediatric ALL,115 and National Cancer Institute/Kite CD28-ζ CAR for diffuse large B cell lymphoma (DLBCL)116 (NCT00924326). Here, CD28 is linked to precursor B-cell acute lymphoblastic leukemia.