REVIEW article
Front. Pharmacol.
Sec. Translational Pharmacology
This article is part of the Research TopicEmerging Targeted and Immunotherapeutic Strategies in Oncology: From Solid Tumors to Hematologic MalignanciesView all 13 articles
Engineering Immunity with CAR-NK Cells: Advancing the Frontiers of Cancer Immunotherapy
Provisionally accepted
- 1Universitatea de Medicina si Farmacie Grigore T Popa lasi, Iași, Romania
- 2Institutul Regional de Oncologie Iasi, Iași, Romania
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Chimeric antigen receptor–modified natural killer (CAR-NK) cells are emerging as a promising alternative to CAR-T therapies, offering advantages such as reduced toxicity, allogeneic feasibility, and flexible manufacturing. Current reviews cover NK biology and CAR engineering progress, yet lack a unified perspective that connects these advances. This review provides a novel synthesis by mapping specific tumor immune evasion mechanisms, including antigen loss, lineage plasticity, impaired antigen processing, epitope masking, and trogocytosis to corresponding next-generation CAR-NK engineering solutions. This "evasion-to-solution" framework highlights how innovations such as dual-antigen CARs, low-affinity designs, NK-specific signaling, iPSC-derived NK platforms, and multiplex gene editing directly mitigate known mechanisms that lead to therapeutic failure. By linking tumor biology to engineering strategy, this review offers a translational roadmap for the rational design of more adaptable and resilient CAR-NK therapies.
Keywords: CAR-NK cell therapy, Immunotherapy, Adoptive Cell immunotherapy (APC), CAR engineering, ICANS - immune effector cell-associated neurotoxicity syndrome, CRS - cytokine release syndrome
Received: 03 Nov 2025; Accepted: 27 Nov 2025.
Copyright: © 2025 Cianga, Antohe, Minciuna and Dăscălescu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ion Antohe
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