Sanomachi Tomomi, Katsuya Yuki, Nakatsura Tetsuya, Koyama Takafumi
Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo 104-0045, Japan.
Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa 277-8577, Japan.
Cancers (Basel). 2025 Jun 11;17(12):1945. doi: 10.3390/cancers17121945.
Chimeric antigen receptor (CAR)-T and T-cell receptor (TCR)-engineered T-cell (TCR-T) therapies have revolutionized the treatment of hematological malignancies; however, their application to solid tumors remains a formidable challenge. The immunosuppressive tumor microenvironment, antigen heterogeneity, and manufacturing complexity limit the clinical efficacy and scalability of these treatment modalities. This review provides a comprehensive analysis of the current clinical development strategies for CAR-T and TCR-T cell therapies for solid tumors. Herein, we discuss recent breakthroughs and highlight the potential of TCR-T cell therapy. Furthermore, innovative approaches for enhancing CAR-T cell function in solid tumors (e.g., in vivo engineering; induced pluripotent stem cell-derived allogeneic CAR-T cells; armored CAR constructs; dual-antigen targeting; and combination regimens with checkpoint inhibitors, chemotherapy, radiotherapy, and oncolytic viruses) are explored. We also present trends in global patent activity, revealing a marked acceleration in CAR-T- and TCR-T-related innovations, with the United States and China leading with respect to application volumes. This field is increasingly characterized by multidisciplinary collaborations between academia and industry, driving the development of next-generation platforms, including messenger RNA-based and off-the-shelf cell therapies. Although no CAR-T product has been approved for solid tumors, these findings underscore the accelerating momentum and translational promise of adoptive cell therapies. Addressing the unique biological and logistical challenges of solid tumors is essential for realizing the full potential of these transformative immunotherapies.
嵌合抗原受体（CAR）-T细胞疗法和经T细胞受体（TCR）工程改造的T细胞（TCR-T）疗法彻底改变了血液系统恶性肿瘤的治疗方式；然而，将它们应用于实体瘤仍然是一项艰巨的挑战。免疫抑制性肿瘤微环境、抗原异质性和生产复杂性限制了这些治疗方式的临床疗效和可扩展性。本综述全面分析了目前用于实体瘤的CAR-T和TCR-T细胞疗法的临床开发策略。在此，我们讨论了最近的突破，并强调了TCR-T细胞疗法的潜力。此外，还探讨了增强实体瘤中CAR-T细胞功能的创新方法（例如，体内工程改造；诱导多能干细胞衍生的同种异体CAR-T细胞；武装CAR构建体；双抗原靶向；以及与检查点抑制剂、化疗、放疗和溶瘤病毒的联合治疗方案）。我们还展示了全球专利活动的趋势，揭示了CAR-T和TCR-T相关创新的显著加速，美国和中国在申请数量方面领先。该领域越来越多地以学术界和产业界之间的多学科合作为特征，推动了下一代平台的发展，包括基于信使核糖核酸的疗法和现成可用的细胞疗法。尽管尚无CAR-T产品被批准用于实体瘤，但这些发现强调了过继性细胞疗法加速发展的势头和转化前景。应对实体瘤独特的生物学和后勤挑战对于充分发挥这些变革性免疫疗法的潜力至关重要。
