Stem cell-derived immune cells in pediatric cancer therapy: From bench to bedside

Figure 1 Overview of stem cell sources and a streamlined workflow for manufacturing immune effector cells. A: Summarizing the main cellular inputs, including induced pluripotent stem cells, hematopoietic stem cells, umbilical cord blood, and adult peripheral blood, highlighting their unique biological features and translational benefits that impact production scalability, product uniformity, and clinical feasibility; B: Illustrating the stepwise manufacturing process, beginning with cell procurement or somatic cell reprogramming, followed by expansion and master cell bank generation, lineage-specific immune differentiation, genetic engineering and functional maturation, good manufacturing practice-compliant quality control, cryopreservation, and final product formulation. Collectively, the figure emphasizes the translational advantages of stem cell-based platforms, including large-scale manufacturability, minimized donor-to-donor variation, reproducible therapeutic products and advanced genetic engineering capabilities that increase immune cell efficacy, durability and safety. iPSCs: Induced pluripotent stem cells; HSCs: Hematopoietic stem cells.

Figure 2 Differentiation frameworks and molecular engineering approaches for stem cell-derived immune cell therapies. Induced pluripotent stem cells are first directed toward hematopoietic progenitors and subsequently differentiated into natural killer cells, T lymphocytes, or dendritic cells using lineage-specific cytokines and organoid- or three-dimensional culture systems, yielding immune populations with robust cytotoxic activity and effective antigen presentation. Targeted molecular modifications - including CRISPR/Cas9-mediated gene editing, cytokine signaling enhancement, CD16 engineering, and the incorporation of controllable safety switches -improve cellular persistence, functional potency, and therapeutic safety. This combined differentiation and engineering strategy supports the scalable generation of highly effective, precisely tailored immune effector cells for advanced immunotherapy applications. NK: Natural killer; iPSCs: Induced pluripotent stem cells; BMP4: Bone morphogenetic protein 4; VEGF: Vascular endothelial growth factor; FLT3 L: Fms-like tyrosine kinase 3 ligand; IL: Interleukin; SCF: Stem cell factor; DC: Dendritic cell; CAR: Chimeric antigen receptor; CISH: Cytokine-inducible SH2-containing protein; 3D: Three-dimensional.