In-depth analysis of the safety of CAR-T cell therapy for solid tumors
In recent years, the rapid progress in oncology, immunology, and molecular biology has dramatically advanced cancer immunotherapy, particularly CAR-T cell therapy. This innovative approach involves engineering a patient’s T cells to express receptors that specifically target tumor antigens, enhancin...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1548979/full |
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| author | Jiayi Dong Jiayi Dong Jiayi Dong Jiayi Dong Jiexiong Wu Ye Jin Ye Jin Ye Jin Ye Jin Ye Jin Zhu Zheng Zhu Zheng Zhu Zheng Zhu Zheng Zhu Zheng Ting Su Ting Su Ting Su Ting Su Ting Su Lijuan Shao Lijuan Shao Lijuan Shao Lijuan Shao Lijuan Shao Jiaxin Bei Jiaxin Bei Jiaxin Bei Jiaxin Bei Size Chen Size Chen Size Chen Size Chen Size Chen |
| author_facet | Jiayi Dong Jiayi Dong Jiayi Dong Jiayi Dong Jiexiong Wu Ye Jin Ye Jin Ye Jin Ye Jin Ye Jin Zhu Zheng Zhu Zheng Zhu Zheng Zhu Zheng Zhu Zheng Ting Su Ting Su Ting Su Ting Su Ting Su Lijuan Shao Lijuan Shao Lijuan Shao Lijuan Shao Lijuan Shao Jiaxin Bei Jiaxin Bei Jiaxin Bei Jiaxin Bei Size Chen Size Chen Size Chen Size Chen Size Chen |
| author_sort | Jiayi Dong |
| collection | DOAJ |
| description | In recent years, the rapid progress in oncology, immunology, and molecular biology has dramatically advanced cancer immunotherapy, particularly CAR-T cell therapy. This innovative approach involves engineering a patient’s T cells to express receptors that specifically target tumor antigens, enhancing their ability to identify and eliminate cancer cells. However, the effectiveness of CAR-T therapy in solid tumors is often hampered by the challenging tumor microenvironment (TME). The complex TME includes dense stroma that obstructs T cell infiltration, abnormal blood vessel structures leading to hypoxia, and an acidic pH, all of which hinder CAR-T cell function. Additionally, the presence of immunosuppressive factors in the TME reduces the efficacy of CAR-T cells, making successful targeting of tumors more difficult. The safety of CAR-T therapy has gained interest, especially CAR-T therapy has shown considerable effectiveness in various cancers, with notable results in multiple myeloma and hepatocellular carcinoma, among others. Nonetheless, CAR-T cell therapy is associated with several adverse reactions primarily driven by heightened levels of proinflammatory cytokines. These reactions include cytokine release syndrome (CRS), neurotoxicity (CANS), and organ toxicity, often leading to serious complications. CRS, characterized by systemic inflammation due to cytokine release, can escalate to severe organ dysfunction. It typically occurs within the first week post-infusion, correlating with CAR-T cell expansion and often presents with fever and hypotension. Meanwhile, CANS encompasses neurological issues ranging from mild symptoms to severe seizures, possibly exacerbated by CRS. Organ toxicity can also arise from CAR-T therapy, with potential damage affecting the gastrointestinal tract, kidneys, liver, and lungs, often tied to shared antigens found in both tumor and healthy tissues. Moreover, long-term effects like cytokine-associated hematotoxicity (CAHT) and secondary malignancies represent significant concerns that could affect the patient’s quality of life post-treatment. The long-term adverse effects and challenges in treating solid tumors underscore the need for ongoing research. Strategies to improve CAR-T cell efficacy, minimize adverse reactions, and enhance patient safety are critical. Future explorations could include designing CAR-T cells to better navigate the TME, identifying specific target antigen profiles to minimize off-target damage, and developing adjunct therapies to mitigate cytokine-related toxicity. Continued monitoring for long-term effects will also be paramount in improving patient outcomes and maintaining their quality of life. Overall, while CAR-T therapy holds great promise, it must be administered with careful consideration of potential side effects and rigorous management strategies to ensure patient safety and treatment efficacy. |
| format | Article |
| id | doaj-art-e93d5f73d09646e98ddf1db4fff4484d |
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| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-e93d5f73d09646e98ddf1db4fff4484d2025-08-20T02:15:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15489791548979In-depth analysis of the safety of CAR-T cell therapy for solid tumorsJiayi Dong0Jiayi Dong1Jiayi Dong2Jiayi Dong3Jiexiong Wu4Ye Jin5Ye Jin6Ye Jin7Ye Jin8Ye Jin9Zhu Zheng10Zhu Zheng11Zhu Zheng12Zhu Zheng13Zhu Zheng14Ting Su15Ting Su16Ting Su17Ting Su18Ting Su19Lijuan Shao20Lijuan Shao21Lijuan Shao22Lijuan Shao23Lijuan Shao24Jiaxin Bei25Jiaxin Bei26Jiaxin Bei27Jiaxin Bei28Size Chen29Size Chen30Size Chen31Size Chen32Size Chen33Department of Immuno-Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaKey Laboratory of Monitoring Adverse Reactions Associated with Chimeric Antigen Receptor T-Cell Therapy, Guangdong Higher Education Institutions, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Engineering Research Center for Precision Medicine in Esophageal Cancer, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaKey Laboratory of Cancer Immunotherapy, Guangdong Higher Education Institutions, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, ChinaDepartment of Immuno-Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaKey Laboratory of Monitoring Adverse Reactions Associated with Chimeric Antigen Receptor T-Cell Therapy, Guangdong Higher Education Institutions, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Engineering Research Center for Precision Medicine in Esophageal Cancer, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaKey Laboratory of Cancer Immunotherapy, Guangdong Higher Education Institutions, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, ChinaDepartment of Immuno-Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaKey Laboratory of Monitoring Adverse Reactions Associated with Chimeric Antigen Receptor T-Cell Therapy, Guangdong Higher Education Institutions, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Engineering Research Center for Precision Medicine in Esophageal Cancer, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaKey Laboratory of Cancer Immunotherapy, Guangdong Higher Education Institutions, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, ChinaDepartment of Immuno-Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaKey Laboratory of Monitoring Adverse Reactions Associated with Chimeric Antigen Receptor T-Cell Therapy, Guangdong Higher Education Institutions, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Engineering Research Center for Precision Medicine in Esophageal Cancer, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaKey Laboratory of Cancer Immunotherapy, Guangdong Higher Education Institutions, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, ChinaDepartment of Immuno-Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaKey Laboratory of Monitoring Adverse Reactions Associated with Chimeric Antigen Receptor T-Cell Therapy, Guangdong Higher Education Institutions, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Engineering Research Center for Precision Medicine in Esophageal Cancer, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaKey Laboratory of Cancer Immunotherapy, Guangdong Higher Education Institutions, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, ChinaDepartment of Immuno-Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaKey Laboratory of Monitoring Adverse Reactions Associated with Chimeric Antigen Receptor T-Cell Therapy, Guangdong Higher Education Institutions, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Engineering Research Center for Precision Medicine in Esophageal Cancer, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaKey Laboratory of Cancer Immunotherapy, Guangdong Higher Education Institutions, Guangdong Pharmaceutical University, Guangzhou, ChinaDepartment of Immuno-Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaKey Laboratory of Monitoring Adverse Reactions Associated with Chimeric Antigen Receptor T-Cell Therapy, Guangdong Higher Education Institutions, Guangdong Pharmaceutical University, Guangzhou, ChinaGuangdong Provincial Engineering Research Center for Precision Medicine in Esophageal Cancer, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, ChinaKey Laboratory of Cancer Immunotherapy, Guangdong Higher Education Institutions, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, ChinaIn recent years, the rapid progress in oncology, immunology, and molecular biology has dramatically advanced cancer immunotherapy, particularly CAR-T cell therapy. This innovative approach involves engineering a patient’s T cells to express receptors that specifically target tumor antigens, enhancing their ability to identify and eliminate cancer cells. However, the effectiveness of CAR-T therapy in solid tumors is often hampered by the challenging tumor microenvironment (TME). The complex TME includes dense stroma that obstructs T cell infiltration, abnormal blood vessel structures leading to hypoxia, and an acidic pH, all of which hinder CAR-T cell function. Additionally, the presence of immunosuppressive factors in the TME reduces the efficacy of CAR-T cells, making successful targeting of tumors more difficult. The safety of CAR-T therapy has gained interest, especially CAR-T therapy has shown considerable effectiveness in various cancers, with notable results in multiple myeloma and hepatocellular carcinoma, among others. Nonetheless, CAR-T cell therapy is associated with several adverse reactions primarily driven by heightened levels of proinflammatory cytokines. These reactions include cytokine release syndrome (CRS), neurotoxicity (CANS), and organ toxicity, often leading to serious complications. CRS, characterized by systemic inflammation due to cytokine release, can escalate to severe organ dysfunction. It typically occurs within the first week post-infusion, correlating with CAR-T cell expansion and often presents with fever and hypotension. Meanwhile, CANS encompasses neurological issues ranging from mild symptoms to severe seizures, possibly exacerbated by CRS. Organ toxicity can also arise from CAR-T therapy, with potential damage affecting the gastrointestinal tract, kidneys, liver, and lungs, often tied to shared antigens found in both tumor and healthy tissues. Moreover, long-term effects like cytokine-associated hematotoxicity (CAHT) and secondary malignancies represent significant concerns that could affect the patient’s quality of life post-treatment. The long-term adverse effects and challenges in treating solid tumors underscore the need for ongoing research. Strategies to improve CAR-T cell efficacy, minimize adverse reactions, and enhance patient safety are critical. Future explorations could include designing CAR-T cells to better navigate the TME, identifying specific target antigen profiles to minimize off-target damage, and developing adjunct therapies to mitigate cytokine-related toxicity. Continued monitoring for long-term effects will also be paramount in improving patient outcomes and maintaining their quality of life. Overall, while CAR-T therapy holds great promise, it must be administered with careful consideration of potential side effects and rigorous management strategies to ensure patient safety and treatment efficacy.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1548979/fullCAR-T cellstumor immunitysolid tumorstumor therapyadverse reactions |
| spellingShingle | Jiayi Dong Jiayi Dong Jiayi Dong Jiayi Dong Jiexiong Wu Ye Jin Ye Jin Ye Jin Ye Jin Ye Jin Zhu Zheng Zhu Zheng Zhu Zheng Zhu Zheng Zhu Zheng Ting Su Ting Su Ting Su Ting Su Ting Su Lijuan Shao Lijuan Shao Lijuan Shao Lijuan Shao Lijuan Shao Jiaxin Bei Jiaxin Bei Jiaxin Bei Jiaxin Bei Size Chen Size Chen Size Chen Size Chen Size Chen In-depth analysis of the safety of CAR-T cell therapy for solid tumors Frontiers in Immunology CAR-T cells tumor immunity solid tumors tumor therapy adverse reactions |
| title | In-depth analysis of the safety of CAR-T cell therapy for solid tumors |
| title_full | In-depth analysis of the safety of CAR-T cell therapy for solid tumors |
| title_fullStr | In-depth analysis of the safety of CAR-T cell therapy for solid tumors |
| title_full_unstemmed | In-depth analysis of the safety of CAR-T cell therapy for solid tumors |
| title_short | In-depth analysis of the safety of CAR-T cell therapy for solid tumors |
| title_sort | in depth analysis of the safety of car t cell therapy for solid tumors |
| topic | CAR-T cells tumor immunity solid tumors tumor therapy adverse reactions |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1548979/full |
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