SynNotch CAR-T cell, when synthetic biology and immunology meet again
Cancer immunotherapy has been transformed by chimeric antigen receptor (CAR) T-cell treatment, which has shown groundbreaking results in hematological malignancies. However, its application in solid tumors remains a formidable challenge due to immune evasion, tumor heterogeneity, and safety concerns...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1545270/full |
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| author | Mohsen Shirzadian Sepideh Moori Reza Rabbani Fatemeh Rahbarizadeh |
| author_facet | Mohsen Shirzadian Sepideh Moori Reza Rabbani Fatemeh Rahbarizadeh |
| author_sort | Mohsen Shirzadian |
| collection | DOAJ |
| description | Cancer immunotherapy has been transformed by chimeric antigen receptor (CAR) T-cell treatment, which has shown groundbreaking results in hematological malignancies. However, its application in solid tumors remains a formidable challenge due to immune evasion, tumor heterogeneity, and safety concerns arising from off-target effects. A long-standing effort in this field has been the development of synthetic receptors to create new signaling pathways and rewire immune cells for the specific targeting of cancer cells, particularly in cell-based immunotherapy. This field has undergone a paradigm shift with the introduction of synthetic Notch (synNotch) receptors, which offer a highly versatile signaling platform modeled after natural receptor-ligand interactions. By functioning as molecular logic gates, synNotch receptors enable precise, multi-antigen regulation of T-cell activation, paving the way for enhanced specificity and control. This review explores the revolutionary integration of synNotch systems with CAR T-cell therapy, emphasizing cutting-edge strategies to overcome the inherent limitations of traditional approaches. We delve into the mechanisms of synNotch receptor design, focusing on their ability to discriminate between cancerous and normal cells through spatiotemporally controlled gene expression. Additionally, we highlight recent advancements to improve therapeutic efficacy, safety, and adaptability in treating solid tumors. This study highlights the potential of synNotch-based CAR-T cells to transform the field of targeted cancer therapy by resolving present challenges and shedding light on potential future paths. |
| format | Article |
| id | doaj-art-b2c3159a5d1348eaa2e8f81132cf460d |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-b2c3159a5d1348eaa2e8f81132cf460d2025-08-20T02:17:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15452701545270SynNotch CAR-T cell, when synthetic biology and immunology meet againMohsen Shirzadian0Sepideh Moori1Reza Rabbani2Fatemeh Rahbarizadeh3Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IranDepartment of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranDepartment of Stem Cell Technology and Tissue Engineering, Faculty of Interdisciplinary Science and Technology, Tarbiat Modares University, Tehran, IranDepartment of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranCancer immunotherapy has been transformed by chimeric antigen receptor (CAR) T-cell treatment, which has shown groundbreaking results in hematological malignancies. However, its application in solid tumors remains a formidable challenge due to immune evasion, tumor heterogeneity, and safety concerns arising from off-target effects. A long-standing effort in this field has been the development of synthetic receptors to create new signaling pathways and rewire immune cells for the specific targeting of cancer cells, particularly in cell-based immunotherapy. This field has undergone a paradigm shift with the introduction of synthetic Notch (synNotch) receptors, which offer a highly versatile signaling platform modeled after natural receptor-ligand interactions. By functioning as molecular logic gates, synNotch receptors enable precise, multi-antigen regulation of T-cell activation, paving the way for enhanced specificity and control. This review explores the revolutionary integration of synNotch systems with CAR T-cell therapy, emphasizing cutting-edge strategies to overcome the inherent limitations of traditional approaches. We delve into the mechanisms of synNotch receptor design, focusing on their ability to discriminate between cancerous and normal cells through spatiotemporally controlled gene expression. Additionally, we highlight recent advancements to improve therapeutic efficacy, safety, and adaptability in treating solid tumors. This study highlights the potential of synNotch-based CAR-T cells to transform the field of targeted cancer therapy by resolving present challenges and shedding light on potential future paths.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1545270/fullsynNotch receptorCAR-T cell therapysynthetic biologyimmunotherapycancermolecular logic-gates |
| spellingShingle | Mohsen Shirzadian Sepideh Moori Reza Rabbani Fatemeh Rahbarizadeh SynNotch CAR-T cell, when synthetic biology and immunology meet again Frontiers in Immunology synNotch receptor CAR-T cell therapy synthetic biology immunotherapy cancer molecular logic-gates |
| title | SynNotch CAR-T cell, when synthetic biology and immunology meet again |
| title_full | SynNotch CAR-T cell, when synthetic biology and immunology meet again |
| title_fullStr | SynNotch CAR-T cell, when synthetic biology and immunology meet again |
| title_full_unstemmed | SynNotch CAR-T cell, when synthetic biology and immunology meet again |
| title_short | SynNotch CAR-T cell, when synthetic biology and immunology meet again |
| title_sort | synnotch car t cell when synthetic biology and immunology meet again |
| topic | synNotch receptor CAR-T cell therapy synthetic biology immunotherapy cancer molecular logic-gates |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1545270/full |
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