Cancer Genetics and Epigenetics, 2025, Vol.13, No.5, 206-214 http://medscipublisher.com/index.php/cge 211 HER2, Claudin18.2 and GD2. Studies targeting HER2 have been carried out in sarcoma and glioblastoma. CAR-T targeting Claudin18.2 has been tested in gastrointestinal cancers, while CAR-T targeting GD2 has shown certain effects in neuroblastoma and other childhood solid tumors (Tony et al., 2025). Although the types of targets are diverse, most trials still use first-generation or second-generation CAR-T products, and there are still relatively few next-generation structures entering clinical evaluation (Sorkhabi et al., 2023; Chen et al., 2024). Worldwide, the number of related clinical trials is constantly increasing, among which China and the United States are leading in the number of studies. Now, more than 40 different antigens have been studied, which indicates that people are constantly seeking ideal targets for solid tumors. However, most of these trials are still at an early stage, mainly focusing on safety and feasibility studies, and have not shown obvious therapeutic effects yet (Sterner and Sterner, 2021; Guzman et al., 2023). 5.2 The partial remission and overall therapeutic effect of the patient remain unsatisfactory Although in some trials, the conditions of some patients have partially improved or no longer deteriorated, the overall effect of CAR-T treatment for solid tumors is still not very satisfactory. Compared with the obvious remission effect in the treatment of blood cancer, the remission of solid tumors often lasts for a short time and has limited effect, and complete remission cases are even rarest (Misawa et al., 2022; Sorkhabi et al., 2023). The reasons for this result include different antigen expressions, weak T cells' ability to enter tumors, and the inhibitory effect of the tumor microenvironment. These circumstances indicate that the design of CAR-T cells still needs further improvement, the method of selecting patients still needs to be refined, and the formulation of combined treatment plans also needs to further enhance the therapeutic effect. The current research focuses include developing new-generation Cars, multi-target strategies and adjuvant therapeutic approaches to overcome existing obstacles and bring more durable therapeutic effects to patients with solid tumors (Guzman et al., 2023; Chen et al., 2024; Khan et al., 2025; Tony et al., 2025). 5.3 Cytokine release syndrome, neurotoxicity and other adverse events The safety of CAR-T treatment for solid tumors still requires high attention. Cytokine release syndrome (CRS) and neurotoxicity are well known in the treatment of hematological malignancies and occur from time to time in solid tumor trials, sometimes leading to serious and even life-threatening consequences (Sorkhabi et al., 2023; Chen et al., 2024; Khan et al., 2025). Since the target antigen is also expressed in normal tissues, off-target toxicity is particularly worthy of attention, which may cause adverse reactions, limit the dosage of medication and affect the therapeutic effect. To reduce these risks, the current measures adopted include adding safety switches, optimizing antigen selection and strengthening patient monitoring. However, how to balance the therapeutic effect and safety remains a major challenge, which also indicates that CAR-T cell modification technology and clinical management need continuous innovation (Dimitri et al., 2022; Guzman et al., 2023; Yan et al., 2023). 6 Future Prospects: CAR-T Cell Therapy for Solid Tumors 6.1 It can be used in combination with adoptive cell therapies such as CAR-NK and TCR-T Combining CAR-T cell therapy with other adoptive cell treatment methods, such as CAR-NK (chimeric antigen receptor natural killer cells) and TCR-T (T cell receptor engineered T cells), is a promising direction for addressing the problems existing in CAR-T treatment of solid tumors. CAR-NK cells have many advantages. For instance, they do not rely on HLA when identifying tumors, have a relatively low risk of triggering graft-versus-host disease, and may be easier to obtain. These characteristics make it very attractive in combination therapy or alternative treatment regimens for solid tumors (Larson et al., 2022). TCR-T cells can recognize intracellular antigens presented by MHC molecules, make up for the deficiencies of CAR-T, expand the targeting range of tumor antigens, and deal with different tumor types (Maalej et al., 2023; Chen et al., 2024). When these methods are used together, they can solve the problem of tumor drug resistance through their respective different ways of action, thereby improving the therapeutic effect. For instance, CAR-NK and CAR-M
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