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Updated: Sep 22, 2025
Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells
Published on: February 14, 2025
Natural killer cells: a promising immunotherapy for cancer
Junfeng Chu1, Fengcai Gao2, Meimei Yan1
1Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan, China.
Abstract:
As a promising alternative platform for cellular immunotherapy, natural killer cells (NK) have recently gained attention as an important type of innate immune regulatory cell. NK cells can rapidly kill multiple adjacent cancer cells through non-MHC-restrictive effects. Although tumors may develop multiple resistance mechanisms to endogenous NK cell attack, in vitro activation, expansion, and genetic modification of NK cells can greatly enhance their anti-tumor activity and give them the ability to overcome drug resistance. Some of these approaches have been translated into clinical applications, and clinical trials of NK cell infusion in patients with hematological malignancies and solid tumors have thus far yielded many encouraging clinical results. CAR-T cells have exhibited great success in treating hematological malignancies, but their drawbacks include high manufacturing costs and potentially fatal toxicity, such as cytokine release syndrome. To overcome these issues, CAR-NK cells were generated through genetic engineering and demonstrated significant clinical responses and lower adverse effects compared with CAR-T cell therapy. In this review, we summarize recent advances in NK cell immunotherapy, focusing on NK cell biology and function, the types of NK cell therapy, and clinical trials and future perspectives on NK cell therapy.
Insights
Natural killer (NK) cell immunotherapy shows promise for cancer treatment, offering enhanced anti-tumor activity and overcoming drug resistance. Engineered CAR-NK cells provide significant clinical responses with fewer adverse effects than CAR-T cell therapy.
Area of Science:
- Immunology
- Cellular Therapy
- Oncology
Background:
- Natural killer (NK) cells are innate immune cells crucial for rapid, non-MHC-restricted cancer cell killing.
- Tumors develop resistance to NK cells, necessitating strategies to enhance their anti-tumor efficacy.
- Existing immunotherapies like CAR-T cells face challenges including high costs and severe toxicities such as cytokine release syndrome.
Purpose of the Study:
- To review recent advancements in NK cell immunotherapy.
- To discuss NK cell biology, function, and therapeutic applications.
- To explore clinical trials and future directions for NK cell-based cancer therapies.
Main Methods:
- Review of current scientific literature on NK cell immunotherapy.
- Analysis of NK cell activation, expansion, and genetic modification techniques.
- Examination of clinical trial data for NK cell therapies in hematological malignancies and solid tumors.
Main Results:
- In vitro manipulation of NK cells significantly boosts their anti-tumor activity and ability to overcome drug resistance.
- Clinical trials demonstrate encouraging results for NK cell infusions in various cancers.
- Chimeric antigen receptor (CAR)-NK cells exhibit potent anti-tumor responses and a favorable safety profile compared to CAR-T cells.
Conclusions:
- NK cell immunotherapy is a rapidly advancing field with significant therapeutic potential.
- CAR-NK cells represent a promising alternative to CAR-T cells, offering improved safety and efficacy.
- Further research and clinical trials are essential to optimize NK cell therapies for broader cancer treatment applications.
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