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:Modulation of Radiation Doses and Chimeric Antigen Receptor T Cells: A Promising New Weapon in Solid Tumors-A Narrative Review.
Modulation of Radiation Doses and Chimeric Antigen Receptor T Cells: A Promising New Weapon in Solid Tumors-A Narrative Review.
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肿瘤行为由其与肿瘤微环境(TME)的相互作用决定。嵌合抗原受体(CAR-T)细胞疗法代表了一种新型的细胞免疫治疗(IT)。免疫细胞对放射治疗(RT)表现出不同的敏感性。RT可以通过改变TME和诱导DNA损伤来影响肿瘤细胞,其效应因低剂量和高剂量的不同而不同,并且可以促进CAR-T 细胞的表达。CAR-T 细胞是患者T细胞经基因工程改造后,能够识别表面结构并根除癌细胞。高剂量放射治疗(HDRT,>10-20 Gy/分次)通过诱导坏死、大规模炎症和死亡,将免疫学上的“冷”肿瘤转化为“热”肿瘤。LDRT(低剂量放射治疗,>5-10 Gy/分次)增加CAR-T 细胞的扩增并导致非免疫原性死亡。一种创新方法,称为LATTICE技术,将高剂量集中于FDG高摄取区域,低剂量作用于肿瘤周边。RT与免疫检查点抑制剂的联合可增强照射部位和未照射部位的肿瘤免疫原性和免疫反应。本叙述性综述的目的是阐明迄今为止关于CAR-T 细胞疗法及其与放射治疗在实体瘤中可能联合应用的认识。
Tumor behavior is determined by its interaction with the tumor microenvironment (TME). Chimeric antigen receptor (CART) cell therapy represents a new form of cellular immunotherapy (IT). Immune cells present a different sensitivity to radiation therapy (RT). RT can affect tumor cells both modifying the TME and inducing DNA damage, with different effects depending on the low and high doses delivered, and can favor the expression of CART cells. CART cells are patients' T cells genetically engineered to recognize surface structure and to eradicate cancer cells. High-dose radiation therapy (HDRT, >10-20 Gy/fractions) converts immunologically "cold" tumors into "hot" ones by inducing necrosis and massive inflammation and death.
LDRT (low-dose radiation therapy, >5-10 Gy/fractions) increases the expansion of CART cells and leads to non-immunogenetic death. An innovative approach, defined as the LATTICE technique, combines a high dose in higher FDG- uptake areas and a low dose to the tumor periphery.
The association of RT and immune checkpoint inhibitors increases tumor immunogenicity and immune response both in irradiated and non-irradiated sites. The aim of this narrative review is to clarify the knowledge, to date, on CART cell therapy and its possible association with radiation therapy in solid tumors.
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