Background: Chimeric Antigen Receptor (CAR) T-cell therapy has transformed the treatment of hematological malignancies, yet its application in solid tumors remains constrained by unique biological and logistical barriers. Objective: This review critically examines the evolving landscape of CAR T-cell therapy in solid malignancies, with a focus on antigen heterogeneity, the immunosuppressive tumor microenvironment, and risks of on-target, off-tumor toxicity. Methods: We outline recent advances in CAR engineering, including co-stimulatory optimization, dual- and multi-antigen targeting, armored CARs, and gene-edited constructs designed to enhance persistence and anti-tumor activity. Clinical progress is highlighted by recent FDA approvals of genetically modified T-cell therapies in synovial sarcoma and melanoma, underscoring the potential for broader solid tumor application. Additionally, we synthesize early-phase clinical trial findings across multiple solid tumor types (e.g., lung, colorectal, ovarian, glioblastoma), and discuss innovative approaches such as regional delivery, checkpoint blockade combinations, and incorporation of chemokine receptors for improved tumor infiltration. The review also considers future strategies, including artificial intelligence-guided target discovery and rational trial design to overcome translational bottlenecks. Conclusions: With expanding clinical experience and continued technological innovation, CAR T-cell therapy is steadily transitioning from an experimental strategy to a therapeutic reality in solid tumors, poised to reshape the future of cancer immunotherapy.
背景：嵌合抗原受体（CAR）T细胞疗法已彻底改变血液系统恶性肿瘤的治疗格局，但其在实体瘤中的应用仍受限于独特的生物学与临床实践障碍。目的：本文系统评述CAR-T细胞疗法在实体瘤领域的最新进展，重点关注抗原异质性、免疫抑制性肿瘤微环境以及靶向/脱靶毒性风险。方法：我们梳理了CAR工程领域的最新突破，包括共刺激结构域优化、双/多抗原靶向系统、装甲型CAR设计以及通过基因编辑技术增强细胞持久性与抗肿瘤活性的策略。临床进展方面，美国食品药品监督管理局近期批准了针对滑膜肉瘤和黑色素瘤的基因修饰T细胞疗法，这为实体瘤的广泛应用奠定了重要基础。此外，我们整合分析了多类实体瘤（如肺癌、结直肠癌、卵巢癌、胶质母细胞瘤）早期临床试验数据，并探讨了区域性给药、免疫检查点抑制剂联合疗法、趋化因子受体修饰增强肿瘤浸润等创新策略。本文还展望了人工智能引导的靶点发现、理性化临床试验设计等未来发展方向，以突破临床转化瓶颈。结论：随着临床经验的积累与技术创新持续推进，CAR-T细胞疗法正从实验性策略逐步转化为实体瘤治疗的现实选择，有望重塑肿瘤免疫治疗的未来格局。
Advancing CAR T-Cell Therapy in Solid Tumors: Current Landscape and Future Directions
肿瘤(癌症)患者之家