For example, the CD28 and 4-1BB co-stimulatory domains of second-generation CARs lead to distinct differentiation states, with the CD28 domain inducing effector-memory T cells, while the 4-1BB domain leads to the formation of central memory cells, making the latter probably better suited for CLL therapy [91]. The gene discussed is CD28; the disease is B-cell chronic lymphocytic leukemia.