Programming T-cell fates for therapeutic use. After antigen encounter or stimulation with anti-CD3 and anti-CD28 antibody-conjugated microbeads, naive T cells (T_N) enter a program of proliferation and differentiation that culminates in the generation of terminally differentiated short-lived effector T cells (T_EFF). During this process of maturation, T cells progressively acquire effector functions but simultaneously lose their capacities for self-renewal and survival, diminishing their therapeutic effectiveness. Cytokines and small molecules can be used to modulate this process and preferentially generate a desired T-cell subset. IL-2 induces effector memory T cells (T_EM), while IL-7 and IL-15 can be used in combination to generate T memory stem cells (T_SCM). T_SCM can also be induced by targeting the Wnt/β-catenin signaling pathway with TWS119 or other inhibitors of GSK-3β. APC indicates antigen presenting cell; and T_CM, central memory T cell.