This general review showed that the available data from clinical trials do not demonstrate a clear advantage of either CD28-costimulated or 4-1BB-costimulated CARs for treating B cell lymphomas or B-ALL, pointing out that more extensive studies and comparative clinical trials must be performed to allow a conclusion about the performance of the different costimulatory domains against B-cell malignancies [74]. This evidence concerns the gene CD28 and acute lymphoblastic leukemia.