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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Biomarkers for prediction of CAR T therapy outcomes: current and future perspectives.
Biomarkers for prediction of CAR T therapy outcomes: current and future perspectives.
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嵌合抗原受体(CAR)T细胞疗法在治疗血液系统恶性肿瘤方面潜力巨大。尽管具有明显获益,该疗法目前仍主要用于二线治疗,原因包括严重副作用和部分患者无应答。全球众多研究者一直试图寻找有效预测性生物标志物,以早期预测CAR-T 治疗结局和不良反应,但迄今成效有限。本综述全面概述预测性生物标志物的现状。尽管现有预测指标与治疗结局存在一定相关性,但它们未能涵盖免疫系统动态的复杂性。本文旨在识别六大类预测性生物标志物,并建议将其用于开发更完善、高效的预测模型,包括线粒体动态变化、内皮细胞活化、中枢神经系统损伤、免疫系统标志物、细胞外囊泡以及抑制性肿瘤微环境。全面理解影响治疗效能的多种因素,有望显著改善CAR-T 治疗过程和患者照护,使这一先进免疫疗法更具吸引力,并使患者治疗过程更加便利、结局更理想。
Chimeric antigen receptor (CAR) T cell therapy holds enormous potential for the treatment of hematologic malignancies. Despite its benefits, it is still used as a second line of therapy, mainly because of its severe side effects and patient unresponsiveness. Numerous researchers worldwide have attempted to identify effective predictive biomarkers for early prediction of treatment outcomes and adverse effects in CAR T cell therapy, albeit so far only with limited success. This review provides a comprehensive overview of the current state of predictive biomarkers. Although existing predictive metrics correlate to some extent with treatment outcomes, they fail to encapsulate the complexity of the immune system dynamics.
The aim of this review is to identify six major groups of predictive biomarkers and propose their use in developing improved and efficient prediction models. These groups include changes in mitochondrial dynamics, endothelial activation, central nervous system impairment, immune system markers, extracellular vesicles, and the inhibitory tumor microenvironment.
A comprehensive understanding of the multiple factors that influence therapeutic efficacy has the potential to significantly improve the course of CAR T cell therapy and patient care, thereby making this advanced immunotherapy more appealing and the course of therapy more convenient and favorable for patients.
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