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Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells
Published on: February 14, 2025
Chimeric antigen receptor-natural killer cells: a promising sword against insidious tumor cells
Tahereh Hojjatipour1, Zahra Sharifzadeh2, Amirhosein Maali2,3
1Department of Hematology and Blood Transfusion, Students Research Center, School of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:
Natural killer (NK) cells are a critical component of innate immunity, particularly in initial cancer recognition and inhibition of additional tumor growth or metastasis propagation. NK cells recognize transformed cells without prior sensitization via stimulatory receptors and rapidly eradicate them. However, the protective tumor microenvironment facilitates tumor escaping via induction of an exhaustion state in immune cells, including NK cells. Hence, genetic manipulation of NK cells for specific identification of tumor-associated antigens or a more robust response against tumor cells is a promising strategy for NK cells' tumoricidal augmentation. Regarding the remarkable achievement of engineered CAR-T cells in treating hematologic malignancies, there is evolving interest in CAR-NK cell recruitment in cancer immunotherapy. Innate functionality of NK cells, higher safety, superior in vivo maintenance, and the off-the-shelf potential move CAR-NK-based therapy superior to CAR-T cells treatment. In this review, we have comprehensively discussed the recent genetic manipulations of CAR-NK cell manufacturing regarding different domains of CAR constructs and their following delivery systems into diverse sources of NK cells. Then highlight the preclinical and clinical investigations of CAR-NK cells and examine the current challenges and prospects as an optimistic remedy in cancer immunotherapy.
Insights
Engineered natural killer (NK) cells, or CAR-NK cells, offer a promising cancer immunotherapy. These cells are genetically modified to better target and destroy tumors, potentially overcoming limitations of current treatments.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Natural killer (NK) cells are vital for innate immunity, recognizing and eliminating cancer cells.
- Tumor microenvironments can induce immune exhaustion, hindering NK cell effectiveness.
- Genetic engineering of NK cells presents a strategy to enhance anti-tumor responses.
Purpose of the Study:
- To review recent advancements in CAR-NK cell manufacturing and applications in cancer immunotherapy.
- To compare CAR-NK cell therapy with existing CAR-T cell treatments.
- To examine the challenges and future prospects of CAR-NK cell therapy.
Main Methods:
- Comprehensive review of genetic manipulation techniques for CAR-NK cell development.
- Analysis of CAR construct designs and delivery systems.
- Evaluation of diverse NK cell sources for CAR engineering.
- Synthesis of preclinical and clinical investigation data.
Main Results:
- CAR-NK cells demonstrate potential for enhanced tumor recognition and eradication.
- CAR-NK therapy offers advantages over CAR-T cells, including innate functionality, safety, in vivo persistence, and off-the-shelf availability.
- Significant progress has been made in CAR-NK cell manufacturing and preclinical/clinical investigations.
Conclusions:
- CAR-NK cell therapy is an emerging and optimistic approach in cancer immunotherapy.
- Further research and development are needed to overcome current challenges and fully realize the potential of CAR-NK cells.
- CAR-NK cells represent a promising alternative to CAR-T cell therapy for various cancers.
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