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

Frank Cichocki, Sjoukje J.C. van der Stegen, Jeffrey S. Miller

Research output: Contribution to journalReview articlepeer-review

52 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)846-855
Number of pages10
JournalBlood
Volume141
Issue number8
DOIs
StatePublished - Feb 23 2023

Bibliographical note

Funding Information:
This work was supported in part by grants from the National Institutes of Health (NIH), National Cancer Institute : CA111412 (J.S.M. and F.C.), CA65493 (J.S.M. and F.C.), CA197292 (J.S.M.); and the NIH, National Heart, Lung, and Blood Institute: HL155150 (F.C.).

Publisher Copyright:
© 2023 The American Society of Hematology

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