Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 206-214 http://medscipublisher.com/index.php/cge 212 (CAR-macrophage) therapies are currently under study. They can help CAR-T better enter solid tumors, improve the tumor microenvironment, and also deliver antigens to T cells. When used in combination with CAR-T, they are expected to exert stronger effects. This combination of multiple methods not only increases the treatment options but also brings more hope to the treatment of patients with solid tumors (Zhang et al., 2022). 6.2 Application of smart switches and adjustable CAR designs The field of synthetic biology is driving CAR-T cell therapy into a new stage of development, mainly through the use of smart switches and adjustable CAR structures. These methods can precisely control the activation, functional maintenance and safety of CAR-T cells, thereby addressing key issues such as the toxicity of accidental damage to normal cells and cytokine release responses (Chen et al., 2024). Intelligent switches include gene switches that can trigger cell suicide, as well as CAR-T cells controlled by small molecules. With the help of these switches, doctors can adjust the activity of CAR-T cells in real time, thereby improving the flexibility and safety of treatment (Tony et al., 2025). The CAR design using logic control and synthetic circuits requires the joint activation of multiple signals to enhance tumor specificity and reduce damage to normal tissues (Ma et al., 2019; Khan et al., 2025). These synthetic biology tools are expected to make CAR-T therapy safer, easier to manage, and better adapted to the complex environment of solid tumors. 6.3 Combining genomics with tumor heterogeneity analysis Personalized and precision medicine is gradually being integrated into the research of CAR-T cell therapy. Genomics and single-cell sequencing technologies can help discover patient-specific tumor antigens and analyze different tumor types, which is of great value for designing more effective and personalized CAR-T products (Chen et al., 2024). Researchers hope to customize CAR-T therapy based on the unique molecular characteristics of patients' tumors, thereby enhancing the accuracy of targeting and therapeutic effects. Combining multi-omics data with artificial intelligence can better infer the expression of antigens and the causes of drug resistance, thereby selecting the most suitable CAR design for different patients (Dagar et al., 2023; Khan et al., 2025). This approach tailored to individual circumstances is expected to enhance clinical treatment outcomes while reducing side effects, marking a significant step forward for solid tumor immunotherapy towards precise tumor treatment. 7 Concluding Remarks CAR-T cell therapy for solid tumors still faces persistent challenges, mainly due to the lack of specific antigens that truly exist only within tumors. As a result, it is difficult to accurately identify tumors and minimize damage to normal tissues. The tumor microenvironment (TME) with inhibitory effects can also seriously affect the treatment outcome. It will prevent T cells from entering tumors, accelerate the rate at which T cells lose their function, and also create metabolic and physical obstacles, restricting the survival and functioning of CAR-T cells. The combination of these factors leads to the relatively poor effect of CAR-T in combating tumors, which also indicates that new methods are urgently needed now to enable CAR-T to fully play its role in the treatment of solid tumors. To address these challenges, researchers are developing CAR designs capable of recognizing multiple antigens to tackle the problems of different tumor antigen types and tumor evasion of recognition. At the same time, CAR-T with "protective effects" will also be adopted, or it will be used in combination with checkpoint inhibitors and other methods to regulate the TME, in order to combat immunosuppression and prolong the time for T cells to function. The methods of combined therapy are also under study, such as combining CAR-T with other cell therapies (like CAR-NK, TCR-T) or conventional treatments. These methods are expected to jointly enhance the therapeutic effect and safety, providing patients with solid tumors with more durable and effective treatment responses. In the future, CAR-T treatment for solid tumors will place greater emphasis on precise treatment based on
RkJQdWJsaXNoZXIy MjQ4ODYzNA==