CAR-T cell persistence is heavily dependent on T cell differentiation, of which there are many T cell subsets. Before encountering their cognate antigen, immature T cells are referred to as naïve T (T n ) cells. After an antigen is encountered, T n cells activate and differentiate into stem cell memory T (T SCM ) cells, central memory T (T CM ) cells, effector memory T (T EM ) cells, or eventually terminal effector T (T EFF ) cells, each with varying implications for CAR-T efficacy . Recent work concluded that T SCM and T CM cells have longer persistence and stronger anti-tumor activity than T EM and T EFF counterparts . Specifically, one clinical trial saw CD19-CAR-modified CD8 + T SCM cells exhibit improved fitness and sustained antitumor responses against systemic ALL . As a result, procedures for the expansion of T cells have been optimized to promote more T SCM and T CM cells. This has been accomplished through the strategies explored below.