Rafii Saeed, Mukherji Deborah, Komaranchath Ashok Sebastian, Khalil Charbel, Iqbal Faryal, Abdelwahab Siddig Ibrahim, Abyad Amin, Abuhelwa Ahmad Y, Gandikota Lakshmikanth, Al-Shamsi Humaid O
Department of Oncology, Mediclinic City Hospital, Dubai P.O. Box 505004, United Arab Emirates.
Emirates Oncology Society, Dubai P.O. Box 6600, United Arab Emirates.
Cancers (Basel). 2025 Sep 3;17(17):2898. doi: 10.3390/cancers17172898.
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.
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.
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.
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.
嵌合抗原受体（CAR）T细胞疗法已经改变了血液系统恶性肿瘤的治疗方式，但其在实体瘤中的应用仍然受到独特的生物学和后勤障碍的限制。
本综述批判性地审视了CAR T细胞疗法在实体恶性肿瘤中不断演变的格局，重点关注抗原异质性、免疫抑制性肿瘤微环境以及靶向非肿瘤毒性的风险。
我们概述了CAR工程的最新进展，包括共刺激优化、双抗原和多抗原靶向、武装CAR以及旨在增强持久性和抗肿瘤活性的基因编辑构建体。近期美国食品药品监督管理局（FDA）批准基因改造的T细胞疗法用于滑膜肉瘤和黑色素瘤突出了临床进展，强调了其在更广泛实体瘤应用中的潜力。此外，我们综合了多种实体瘤类型（如肺癌、结直肠癌、卵巢癌、胶质母细胞瘤）的早期临床试验结果，并讨论了如区域给药、检查点阻断联合以及引入趋化因子受体以改善肿瘤浸润等创新方法。该综述还考虑了未来的策略，包括人工智能引导的靶点发现和合理的试验设计以克服转化瓶颈。
随着临床经验的不断积累和技术的持续创新，CAR T细胞疗法正在稳步从一种实验性策略转变为实体瘤治疗的现实手段，有望重塑癌症免疫治疗的未来。
