Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 136-144 http://medscipublisher.com/index.php/cge 141 Sterner and Sterner, 2021; Chen et al., 2022; Hashem et al., 2023). Some patients have achieved long-term remission of their conditions, while others have poor treatment outcomes or even no response at all. This makes it difficult to predict the treatment results in advance and to select the best treatment plan. Current research is dedicated to seeking biomarkers that can predict therapeutic effects and applying advanced technologies such as single-cell RNA sequencing and artificial intelligence to attempt to identify which patients are more suitable for CAR-T therapy. Despite many efforts, due to the lack of reliable predictive tools, clinical treatment decisions and the formulation of personalized treatment plans still face great difficulties (Sterner and Sterner, 2021; Hashem et al., 2023). 5.3 High cost and time-consuming preparation restrict large-scale application CAR-T cell therapy is not only expensive, but also its preparation process is very complex and time-consuming. Due to the need to collect patients' own cells for personalized treatment, as well as complete genetic modification and strict quality inspection, the production cycle is long and the demand for resources is huge (Sterner and Sterner, 2021; Hashem et al., 2023; Merhi et al., 2023). These factors have restricted the promotion and popularization of CAR-T therapy, and the problem is particularly prominent in areas with insufficient medical resources. To address these issues, researchers are exploring the development of universal "off-the-shelf" allogeneic CAR-T products and simplifying the preparation techniques. However, before these innovative achievements are widely applied, the high cost and complex preparation process will still hinder the large-scale use of CAR-T therapy in the treatment of hematological malignancies (Sterner and Sterner, 2021; Hashem et al., 2023; Merhi et al., 2023). 6 Emerging Strategies and Technological Innovations 6.1 New design strategies: multi-targeting, dual-CAR and switchable CAR-T cells Researchers are developing innovative CAR-T cell designs to overcome problems such as antigen escape and poor therapeutic effect. Multi-target and dual-CAR technologies enable T cells to recognize multiple tumor antigens. As a result, the possibility of disease recurrence due to the disappearance of antigens is reduced, and the tumor clearance effect is also better (Sterner and Sterner, 2021). The switchable CAR-T cells are equipped with switches based on synthetic biology, which can control the activity of CAR-T cells from the outside. Doctors can adjust or stop the treatment according to the situation. When serious side effects occur, they can respond in time, and the safety is greatly improved (Hackett et al., 2019; Wang et al., 2025). There are also some new strategies, such as the use of biological guide scaffolds, nanomaterials and oncolytic viruses, to help CAR-T cells move, permeate and function better in the tumor environment. These cross-disciplinary methods are aimed at breaking the immune resistance of tumors, improving the therapeutic effect, and laying the foundation for the development of a new generation of more effective and safer CAR-T therapies (Hackett et al., 2019; Sterner and Sterner, 2021; Wang et al., 2025). 6.2 "Off-the-shelf" allogeneic CAR-T and IPSC-derived CAR-T products To address the issues of practical operation and cost in autologous CAR-T therapy, researchers set out to develop "off-the-shelf" allogeneic CAR-T products, which are derived from healthy donors or induced pluripotent stem cells (iPSCs) (Gao et al., 2020). This universal CAR-T cell can be prepared and stored in advance for use by multiple patients, which can significantly shorten the production time and reduce costs (Merhi et al., 2023; Dipersio and Ali, 2024). Allogeneic and IPSC-derived CAR-T cells are also expected to achieve large-scale and standardized production, enabling more patients to access this treatment and achieving more stable therapeutic effects. However, such therapies also face problems such as graft-versus-host disease and immune rejection. The current research focus is to enhance the safety of these products through means such as gene editing, so that they can exert a more lasting effect in patients (Gao et al., 2020; Merhi et al., 2023; Dipersio and Ali, 2024). 6.3 Combination therapy: combined chemotherapy, radiotherapy or immune checkpoint inhibitors Combining CAR-T cell therapy with other treatment methods is a new strategy that can enhance therapeutic
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