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Review
. 2023 Feb 23;141(8):846-855.
doi: 10.1182/blood.2022016205.

Engineered and banked iPSCs for advanced NK- and T-cell immunotherapies

Frank Cichocki  1 , Sjoukje J C van der Stegen  2   3 , Jeffrey S Miller  1
Affiliations
Review

Engineered and banked iPSCs for advanced NK- and T-cell immunotherapies

Frank Cichocki et al. Blood. .

Abstract

The development of methods to derive induced pluripotent stem cells (iPSCs) has propelled stem cell research, and has the potential to revolutionize many areas of medicine, including cancer immunotherapy. These cells can be propagated limitlessly and can differentiate into nearly any specialized cell type. The ability to perform precise multigene engineering at the iPSC stage, generate master cell lines after clonal selection, and faithfully promote differentiation along natural killer (NK) cells 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 highlight the recent progress in iPSC editing and guided differentiation in the development of NK- and T-cell products for immunotherapy. We 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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Conflict of interest statement

Conflict-of-interest disclosure: F.C. and J.S.M. are paid consultants for Fate Therapeutics, receive stock options, and research funds from this relationship. S.J.C.v.d.S. receives research funds from Fate Therapeutics. These conflicts have been disclosed to the University of Minnesota and Memorial Sloan Kettering Cancer Center who manage this conflict according to institutional policy.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Off-the-shelf hematopoietic cell products derived from renewable engineered pluripotent cell lines. Schematic of the overall approach to generate iNK and iT cells from engineered iPSCs. Figure generated using BioRender.
Figure 2.
Figure 2.
Gene edits for enhancing iPSC-derived NK and T cell function. Strategies for enhancing cytotoxic function, supporting persistence, and avoiding alloreactivity through genetic engineering in the generation of iPSC-derived NK and T cells.
See this image and copyright information in PMC

Comment in

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