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Updated: May 20, 2025

Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells
Published on: February 14, 2025
Breaking barriers: CAR-NK cell therapy breakthroughs in female-related cancers
Ghorbani Vanan Ahmad1, Samaneh Nouri2, Amirhossein Mohammad Gholian2
1Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Abstract:
Cancer stands as a leading cause of mortality globally. The main female-related malignancies are breast cancer, with 2.3 million new cases annually, and ovarian cancer, with 300,000 new cases per year worldwide. The current treatments like surgery, chemotherapy, and radiation therapy have presumably had deficiencies in sustaining long-term anti-tumor responses. Cellular immunotherapy, also referred to as adoptive cell therapy, has shown encouraging advances by employing genetically modified immune cells in fighting cancer by engineering chimeric antigen receptors (CARs) mainly on T cells and natural killer (NK) cells. Studies in NK cell therapies involve unmodified NK cells and CAR-NK cell therapies, targeting cancer cells while limiting the destruction of normal cells. CAR-NK cells represent the next generation of therapeutic immune cells that have been shown to eliminate malignancies through CAR-dependent and CAR-independent mechanisms. They also represent possible candidates for "off-the-shelf" therapies due to their advantages, including the ability to target cancer cells independently of the major histocompatibility complex, reduced risk of alloreactivity, and fewer severe toxicities compared to CAR-T cells. To date, there have been no comprehensive review studies examining the therapeutic potential of CAR-NK cell therapy specifically for female-related malignancies, such as breast and ovarian cancers. This review offers a thorough exploration of CAR-NK cell therapy in relation to these cancers and their responses to treatment.
Insights
Chimeric antigen receptor (CAR)-NK cell therapy shows promise for treating breast and ovarian cancers. This advanced immunotherapy offers a potential "off-the-shelf" treatment option with fewer toxicities than CAR-T cells.
Area of Science:
- Immunology
- Oncology
- Cellular Therapy
Background:
- Breast and ovarian cancers are leading causes of mortality in women, with current treatments having limitations.
- Cellular immunotherapies, particularly chimeric antigen receptor (CAR)-engineered T (CAR-T) and natural killer (NK) cells, are emerging as promising cancer treatments.
- CAR-NK cells offer potential advantages over CAR-T cells, including reduced alloreactivity and toxicity, and suitability for "off-the-shelf" applications.
Purpose of the Study:
- To conduct a comprehensive review of CAR-NK cell therapy specifically for female-related malignancies.
- To explore the therapeutic potential and treatment responses of CAR-NK cell therapy in breast and ovarian cancers.
Main Methods:
- Review of existing literature on CAR-NK cell therapy.
- Analysis of CAR-NK cell mechanisms, including CAR-dependent and CAR-independent pathways.
- Examination of CAR-NK cell applications in preclinical and clinical studies for breast and ovarian cancers.
Main Results:
- CAR-NK cells demonstrate efficacy in targeting and eliminating cancer cells through multiple mechanisms.
- CAR-NK cell therapy presents a viable alternative for treating breast and ovarian cancers, with potential for improved safety and efficacy.
- The review highlights the unique advantages of CAR-NK cells, such as MHC-independent targeting and reduced risk of graft-versus-host disease.
Conclusions:
- CAR-NK cell therapy is a rapidly advancing field with significant potential for treating female-related malignancies.
- Further research and clinical trials are warranted to optimize CAR-NK cell therapy for breast and ovarian cancers.
- CAR-NK cells represent a next-generation immunotherapy with the potential to overcome limitations of current cancer treatments.
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