Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy
Currently, CAR-T cell therapy is known as an efficacious treatment for patients with relapsed/refractory hematologic malignancies. Nonetheless, this method faces several bottlenecks, including low efficacy for solid tumors, lethal adverse effects, high cost of autologous products, and the risk of Gv...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2024.1511931/full |
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| author | Fatemeh Dehghan Yekta Metanat Mandana Askarizadeh Ehsan Ahmadi Vahid Moradi |
| author_facet | Fatemeh Dehghan Yekta Metanat Mandana Askarizadeh Ehsan Ahmadi Vahid Moradi |
| author_sort | Fatemeh Dehghan |
| collection | DOAJ |
| description | Currently, CAR-T cell therapy is known as an efficacious treatment for patients with relapsed/refractory hematologic malignancies. Nonetheless, this method faces several bottlenecks, including low efficacy for solid tumors, lethal adverse effects, high cost of autologous products, and the risk of GvHD in allogeneic settings. As a potential alternative, CAR-NK cell therapy can overcome most of the limitations of CAR-T cell therapy and provide an off-the-shelf, safer, and more affordable product. Although published results from preclinical and clinical studies with CAR-NK cells are promising, several bottlenecks must be unlocked to maximize the effectiveness of CAR-NK cell therapy. These bottlenecks include low in vivo persistence, low trafficking into tumor sites, modest efficacy in solid tumors, and sensitivity to immunosuppressive tumor microenvironment. In recent years, advances in gene manipulation tools and strategies have laid the groundwork to overcome the current bottlenecks of CAR-NK cell therapy. This review will introduce the existing gene manipulation tools and discuss their advantages and disadvantages. We will also explore how these tools can enhance CAR-NK cell therapy’s safety and efficacy. |
| format | Article |
| id | doaj-art-9940b5462b184c32a8ba5a5a1e423a6b |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-9940b5462b184c32a8ba5a5a1e423a6b2025-02-11T06:59:32ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-02-011210.3389/fcell.2024.15119311511931Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapyFatemeh Dehghan0Yekta Metanat1Mandana Askarizadeh2Ehsan Ahmadi3Vahid Moradi4Department of Anatomy and Molecular Biology, Shahid Sadoughi University of Medical Sciences, Yazd, IranFaculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Sistan and Baluchestan Province, IranSchool of Biology and Ecology, University of Maine, Orono, ME, United StatesDepartment of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Hematology and Blood Transfusion Sciences, School of Allied Medicine, Tehran University of Medical Sciences, Tehran, IranCurrently, CAR-T cell therapy is known as an efficacious treatment for patients with relapsed/refractory hematologic malignancies. Nonetheless, this method faces several bottlenecks, including low efficacy for solid tumors, lethal adverse effects, high cost of autologous products, and the risk of GvHD in allogeneic settings. As a potential alternative, CAR-NK cell therapy can overcome most of the limitations of CAR-T cell therapy and provide an off-the-shelf, safer, and more affordable product. Although published results from preclinical and clinical studies with CAR-NK cells are promising, several bottlenecks must be unlocked to maximize the effectiveness of CAR-NK cell therapy. These bottlenecks include low in vivo persistence, low trafficking into tumor sites, modest efficacy in solid tumors, and sensitivity to immunosuppressive tumor microenvironment. In recent years, advances in gene manipulation tools and strategies have laid the groundwork to overcome the current bottlenecks of CAR-NK cell therapy. This review will introduce the existing gene manipulation tools and discuss their advantages and disadvantages. We will also explore how these tools can enhance CAR-NK cell therapy’s safety and efficacy.https://www.frontiersin.org/articles/10.3389/fcell.2024.1511931/fullCAR-NKchimeric antigen receptor (CAR)genetic engineeringgene editingimmunotherapyCRISPR/Cas9 |
| spellingShingle | Fatemeh Dehghan Yekta Metanat Mandana Askarizadeh Ehsan Ahmadi Vahid Moradi Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy Frontiers in Cell and Developmental Biology CAR-NK chimeric antigen receptor (CAR) genetic engineering gene editing immunotherapy CRISPR/Cas9 |
| title | Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy |
| title_full | Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy |
| title_fullStr | Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy |
| title_full_unstemmed | Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy |
| title_short | Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy |
| title_sort | novel gene manipulation approaches to unlock the existing bottlenecks of car nk cell therapy |
| topic | CAR-NK chimeric antigen receptor (CAR) genetic engineering gene editing immunotherapy CRISPR/Cas9 |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2024.1511931/full |
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