Kwon Nayoung, Chen Yvonne Y
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Chemical and Biomolecular Engineering, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Parker Institute for Cancer Immunotherapy Center at UCLA, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Trends Cancer. 2025 Oct;11(10):1019-1029. doi: 10.1016/j.trecan.2025.08.009. Epub 2025 Sep 11.
Chimeric antigen receptor (CAR)-T cell therapy has shown significant clinical benefit in hematologic malignancies but remains less effective in solid tumors due to multiple barriers, including limited tumor infiltration, immunosuppressive microenvironments, and heterogeneity or imperfect specificity in tumor-antigen expression. 'Armoring' CAR-T cells to express chemokine receptors, enzymes that degrade extracellular matrix components, proinflammatory cytokines, or factors that modulate immunosuppressive signals could empower CAR-T cells to overcome barriers associated with solid tumors. However, translating promising preclinical results into reliable clinical benefit for patients with solid tumors remains challenging. This review critically examines emerging CAR-T cell armoring approaches and highlights key translational hurdles and the need for innovations in human-relevant disease models, safety designs, and treatment strategies for effective translation.
嵌合抗原受体（CAR）-T细胞疗法在血液系统恶性肿瘤中已显示出显著的临床益处，但由于多种障碍，包括肿瘤浸润受限、免疫抑制微环境以及肿瘤抗原表达的异质性或特异性不完善，在实体瘤中仍然效果较差。使CAR-T细胞“武装”以表达趋化因子受体、降解细胞外基质成分的酶、促炎细胞因子或调节免疫抑制信号的因子，可以使CAR-T细胞有能力克服与实体瘤相关的障碍。然而，将有前景的临床前结果转化为实体瘤患者可靠的临床益处仍然具有挑战性。本综述批判性地审视了新兴的CAR-T细胞武装方法，并强调了关键的转化障碍，以及在与人类相关的疾病模型、安全性设计和治疗策略方面进行创新以实现有效转化的必要性。
