CD28 and acute lymphoblastic leukemia: Thus, this CD19-focused work has taught us important intricacies to CAR engineering: While CD19 CAR constructs containing either 4-1BB or CD28 costimulatory domains are capable of inducing clinical remissions in a majority of B-ALL patients, only those CARs containing 4-1BB signaling domains appear to induce the long-term persistence essential for durable remissions.