In-depth analysis of the safety of CAR-T cell therapy for solid tumors

作者：Jiayi Dong, Jun Wu, Jin Ye, Zheng Zhu, Ting Su, Lijuan Shao, Jiaxin Bei, Size Chen · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1548979 · 被引用次数：9 · 研究领域：CAR-T cell therapy research、Biomedical and Engineering Education、Biomedical Ethics and Regulation

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, corre...