Immune cell development from human pluripotent stem cells

The landmark derivation of induced pluripotent stem cells (iPSCs) sparked an enormous range of research on development of diverse cell populations. Perhaps no aspect of this work has been as productive as studies on blood and immune cell production. Indeed, essentially all human blood cell populations can be derived from human iPSCs. While derivation of transplantable hematopoietic stem cells (HSCs) from iPSCs has been relatively challenging, clinical translation of iPSC-derived immune cells has been particularly productive. Notably, more patients have been treated with iPSC-derived natural killer (NK) cells than any other iPSC-derived cell type. Use of iPSCs provides a key platform to incorporate multiplexed gene edits before differentiation, enabling NK cells to be engineered with tumor-targeting CARs, cytokine support for improved persistence, enhanced tumor trafficking, and resistance to host immune rejection, modifications uniformly expressed across the entire cellular product. While T cells, macrophages and other immune cells can be produced from human iPSCs, iPSC-derived NK cells have been the most widely used in clinical trials for treatment of refractory malignancies, as well as autoimmune disease. This review summarizes research with a focus on clinical translation of iPSC-derived immune cells, as well as highlights continued challenges and prospects of this field.