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Updated: Oct 9, 2025
Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells
Published on: February 14, 2025
Current Perspectives on "Off-The-Shelf" Allogeneic NK and CAR-NK Cell Therapies
Erica L Heipertz1, Evan R Zynda2, Tor Espen Stav-Noraas3
1Cell & Gene Therapy, Thermo Fisher Scientific, Frederick, MD, United States.
Abstract:
Natural killer cells (NK cells) are the first line of the innate immune defense system, primarily located in peripheral circulation and lymphoid tissues. They kill virally infected and malignant cells through a balancing play of inhibitory and stimulatory receptors. In pre-clinical investigational studies, NK cells show promising anti-tumor effects and are used in adoptive transfer of activated and expanded cells, ex-vivo. NK cells express co-stimulatory molecules that are attractive targets for the immunotherapy of cancers. Recent clinical trials are investigating the use of CAR-NK for different cancers to determine the efficiency. Herein, we review NK cell therapy approaches (NK cell preparation from tissue sources, ways of expansion ex-vivo for "off-the-shelf" allogeneic cell-doses for therapies, and how different vector delivery systems are used to engineer NK cells with CARs) for cancer immunotherapy.
Insights
Natural killer (NK) cell therapy shows promise for cancer immunotherapy. This review covers NK cell preparation, expansion, and engineering with CARs for enhanced anti-tumor activity.
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- Natural killer (NK) cells are crucial innate immune cells targeting infected and malignant cells.
- NK cells utilize a balance of inhibitory and stimulatory receptors for target cell recognition and elimination.
- Pre-clinical studies demonstrate NK cell potential in adoptive transfer for cancer treatment.
Purpose of the Study:
- To review current NK cell therapy approaches for cancer immunotherapy.
- To discuss methods for NK cell preparation and ex-vivo expansion for allogeneic cell therapies.
- To explore vector delivery systems for engineering NK cells with chimeric antigen receptors (CARs).
Main Methods:
- Review of pre-clinical and clinical literature on NK cell therapy.
- Analysis of NK cell isolation and expansion techniques.
- Examination of CAR engineering strategies and vector systems for NK cells.
Main Results:
- NK cells exhibit potent anti-tumor effects, making them attractive for immunotherapy.
- Ex-vivo expansion enables the generation of "off-the-shelf" allogeneic NK cell doses.
- CAR-NK cell therapies are under investigation in clinical trials for various cancers.
Conclusions:
- NK cell therapy, particularly CAR-NK, represents a promising avenue for cancer immunotherapy.
- Standardized methods for NK cell preparation and expansion are essential for therapeutic efficacy.
- Advancements in vector delivery systems are key to successful CAR-NK cell engineering.
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