Redifferentiation of Adaptive Naïve-Like CTL from T-Cell-Derived iPSC

In this chapter, we describe redifferentiation procedures from iPSCs to CD8αβ⁺ cytotoxic T cells in 10 T1/2 and OP9/DL1 feeder condition. iPSC used here is derived from T-cell clone (T-iPSC), which has lost naïve phenotype and acquired exhaustion/senescence phenotype during cloning process (Note 1). On the other hand, redifferentiated T cells (T-iPSC-Ts) reacquire naïve phenotype (CD45RA⁺CD45RO^-CCR7⁺CD62L⁺), which are reportedly critical for in vivo persistence of infused T cells and greatly affect therapeutic efficacy of adoptive immunotherapy. Indeed, T-iPSC-Ts exhibit much superior proliferative capacity while retaining equivalent effector function compared to parental T-cell clones. Here, we demonstrate the methodology to produce naïve-like T-iPSC-Ts, which could be potent cell source for adoptive immunotherapy.