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Review
. 2025 Aug 5:102282.
doi: 10.1016/j.xcrm.2025.102282. Online ahead of print.

Multiplexed iPSC platform for advanced NK cell immunotherapies

Akhilesh Kumar  1 , Colin Fischer  2 , Frank Cichocki  1 , Jeffrey S Miller  3
Affiliations
Review

Multiplexed iPSC platform for advanced NK cell immunotherapies

Akhilesh Kumar et al. Cell Rep Med. .

Abstract

Human pluripotent stem cell (PSC) derivation advances have revealed enormous potential for improved cancer immunotherapy and clinical-scale blood cell production. PSCs can self-renew indefinitely and be differentiated into specialized cells, making them promising candidates for producing cytotoxic lymphocytes. Deriving natural killer (NK) cells from PSCs unlocks new possibilities for studying developmental hematopoiesis and investigating potential immunotherapy treatments. Cellular therapies, combined with genetic engineering, are potent tools for combating cancer and viral infections. While NK cells directly lyse tumor cells, genetic modifications, such as chimeric antigen receptor (CAR) engineering or the deletion of checkpoint molecules, can enhance their functional capacity. Here, we discuss recent advances in induced PSC (iPSC) editing and guided differentiation, focusing on developing NK cell immunotherapeutic products and optimizing iPSCs as an NK cell source to broaden therapeutic options and address diverse patient needs. This comprehensive review evaluates iPSC-derived NK cell-based therapies, recent advances, and future genome-editing strategies.

Keywords: chimeric antigen receptor; gene editing; genetic engineering; immunotherapy; induced pluripotent stem cells; natural killer cells.

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Conflict of interest statement

Declaration of interests J.S.M. and F.C. consult for, receive research support from, and hold stock options in Fate Therapeutics, an iPSC company. J.S.M. also consults for, receives research support from, and holds stock options in GT Biopharma, an NK cell engager company, and advises for Sanofi and Vycellix. These interests have been reviewed and managed by the University of Minnesota in accordance with its conflict-of-interest policy.