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Updated: May 28, 2025
Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells
Published on: February 14, 2025
Differentiating Induced Pluripotent Stem Cells into Natural Killer Cells for Adoptive Cell
Tatiana Budagova1, Anna Efremova1,2, Natalia Usman3
1Research Centre for Medical Genetics, Moskvorechye Str. 1, Moscow 115522, Russia.
Abstract:
Cancers constitute a leading cause of mortality. Chimeric antigen receptor (CAR) cell therapies provide breakthrough solutions for various cancers while posing considerable risks of immunological side reactions. Of various cytotoxic lymphocyte subsets, natural killer (NK) cells are considered the least immunogenic. Obtaining viable NK cells with stable phenotypes in quantities sufficient for modification is technologically challenging. The candidate sources include primary mononuclear cell cultures and immortalized NK cell lines; alternatively, the clinical-grade NK cells can be differentiated from induced pluripotent stem cells (iPSCs) by a good manufacturing practice (GMP)-compatible xeno-free protocol. In this review, we analyze existing protocols for targeted differentiation of human iPSCs into NK cells with a focus on xeno-free requirements.
Insights
Natural killer (NK) cell therapy offers a promising cancer treatment with fewer side effects. This review examines methods for producing clinical-grade NK cells from induced pluripotent stem cells (iPSCs) using xeno-free protocols.
Area of Science:
- Immunology
- Cell Therapy
- Stem Cell Biology
Background:
- Cancer immunotherapy, including CAR T-cell therapy, faces challenges with immunogenic side effects.
- Natural killer (NK) cells are less immunogenic cytotoxic lymphocytes, making them attractive for cell therapy.
- Current methods for obtaining sufficient, stable NK cells for therapeutic modification are limited.
Purpose of the Study:
- To review protocols for differentiating human induced pluripotent stem cells (iPSCs) into natural killer (NK) cells.
- To focus on xeno-free methods for generating clinical-grade NK cells suitable for therapeutic applications.
- To address the technological challenges in producing large quantities of viable NK cells.
Main Methods:
- Analysis of existing scientific literature on iPSC differentiation into NK cells.
- Evaluation of protocols based on xeno-free requirements and Good Manufacturing Practice (GMP) compatibility.
- Comparison of different sources for NK cell generation, including primary cultures and cell lines.
Main Results:
- Induced pluripotent stem cells (iPSCs) can be differentiated into NK cells.
- Xeno-free protocols offer a pathway to clinical-grade NK cell production.
- Challenges remain in achieving sufficient cell yield and stable phenotypes.
Conclusions:
- Differentiating iPSCs via xeno-free protocols is a viable strategy for generating clinical-grade NK cells for cancer therapy.
- Further optimization is needed to overcome challenges in cell quantity and stability.
- NK cell therapy holds significant potential for safer cancer treatment.
