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Engineered and Banked iPSCs for advanced NK and T cell immunotherapies.

Frank CichockiSjoukje J C van der SteganJeffrey S Miller
Published in: Blood (2022)
The development of methods to derive induced pluripotent stem cells (iPSCs) has propelled stem cell research forward and has the potential to revolutionize many areas of medicine including cancer immunotherapy. These cells can be propagated limitlessly and differentiated into nearly any specialized cell type. The ability to perform precise multi-gene engineering at the iPSC stage, generate master cell lines after clonal selection, and faithfully promote differentiation along the natural killer (NK) cell and T cell lineages is now leading to new opportunities for the administration of off-the-shelf cytotoxic lymphocytes with direct antigen targeting to treat patients with relapsed/refractory cancer. In this review, we will highlight recent progress in iPSC editing and guided differentiation to develop NK and T cell products for immunotherapy. We will also discuss some of the potential barriers that remain in unleashing the full potential of iPSC-derived cytotoxic effector cells in the adoptive transfer setting and how some of these limitations may be overcome through gene editing.
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