CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Barriers and Strategies to Enhance CAR-T Cell Infiltration in Solid Tumours: A Systematic Review.
Barriers and Strategies to Enhance CAR-T Cell Infiltration in Solid Tumours: A Systematic Review.
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CAR-T(CAR-T)细胞疗法革新了血液系统恶性肿瘤治疗,并实现持久而强效的应答。然而,CAR-T 细胞用于实体瘤仍受复杂障碍网络限制,其中最突出的是肿瘤浸润不足。主要障碍包括趋化因子与受体不匹配、肿瘤血管异常、免疫抑制性细胞群(如髓源性抑制细胞、肿瘤相关巨噬细胞和调节性T细胞)、癌相关成纤维细胞及细胞外基质形成的致密网络、T细胞功能障碍和耗竭、肿瘤微环境中的代谢限制、肿瘤异质性,以及与肿瘤位置有关的运输限制。本综述整合机制认识与创新生物工程和联合治疗方法,系统阐述限制CAR-T 细胞浸润的因素,并重点介绍提高实体瘤治疗疗效、持久性和侵入能力的转化策略。
Chimeric antigen receptor T (CAR-T) cell therapy has revolutionised the treatment of hematologic malignancies, achieving durable and robust responses.
However, the application of CAR-T cells in solid tumours remains limited by a complex network of barriers, most notably poor tumour infiltration. The key obstacles include mismatch between chemokines and receptors, abnormal tumour vasculature, immunosuppressive cellular populations (such as myeloid-derived suppressor cells, tumour-associated macrophages and regulatory T cells), dense network of cancer-associated fibroblasts and extracellular matrix, T cell dysfunction and exhaustion, metabolic limitations within the tumour microenvironment, tumour heterogeneity and transport limitations related to tumour location.
By integrating mechanistic insights with innovative bioengineering and combination approaches, this review systematically elaborates on the factors that limit the infiltration of CAR-T cells and emphasises transformation strategies for improving the efficacy, durability and invasiveness of treating solid tumours.
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