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Microbes & Immunity iPSC-derived NK cell immunotherapy

Figure 2. Overcoming microenvironmental barriers and enhancing NK cell antitumor activity through gene editing
Abbreviations: CAR: Chimeric antigen receptor; CXCR: C-X-C motif chemokine receptor; GzmB: granzyme B; IL: Interleukin; iPSC: Induced pluripotent
stem cells; NK: Natural killer; KIR: killer-cell immunoglobulin-like receptor; PBMC: peripheral blood mononuclear cells. Figure created by the authors.

5. Concluding remarks quality control, and differentiation processes are complex
and time-consuming, making personalized production
NK cells possess the remarkable ability to target and prohibitively expensive. Consequently, allogeneic iPSCs-
eliminate both tumor cells and virus-infected cells.
Adoptive transplantation of NK cells exhibits exceptional derived NK cells are primarily used, but they may cause
potential damage to the recipient’s normal cells and face
efficacy in combatting hematologic tumors. However, their rejection by the recipient. The extended differentiation
application in the treatment of solid tumors is limited.
Recent years have witnessed the development of numerous time of iPSC-derived NK cells leads to prolonged
strategies aimed at bolstering and adapting NK cells to preparation cycles, presenting challenges in maintaining
surmount this limitation. Even though CAR-T cell therapy process stability and batch consistency. In addition,
has yielded promising clinical results, CAR-NK cells variability among iPSCs from different sources affects
have also gained prominence within the realm of cancer the comparability of data across various laboratories.
immunotherapy. Nonetheless, it is becoming increasingly Addressing these challenges is crucial, as it would greatly
apparent that CAR-NK cells may not represent the ultimate enhance the potential of NK cells in cancer treatment by
solution for adoptive NK cell therapy. The imperative lies in improving their safety and efficacy, thus offering more
tailoring NK cell therapies to fully exploit their distinctive effective therapeutic options for patients.
attributes. Acknowledgments

NK cells derived from iPSCs have pioneered a new
frontier in NK cell-based tumor immunotherapy strategies. None.
These cells have been genetically engineered to incorporate Funding
CARs, enhance their ADCC, and enable autocrine secretion
of cytokine. However, these cells also face numerous This work was supported by the National Key Research
challenges in clinical applications, including issues with and Development Plan of China (2022YFF1202901),
allogeneic rejection. While autologous iPSCs could be and the National Nature Scientific Foundation of China
employed, the reprogramming, selection, establishment, (82372801).

Volume 2 Issue 1 (2025) 36 doi: 10.36922/mi.5653