决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Predictive Models for Toxicities after CAR T-cell Therapy: Challenges and Opportunities.
Predictive Models for Toxicities after CAR T-cell Therapy: Challenges and Opportunities.
未标注:嵌合抗原受体(CAR)T 细胞疗法的应用日益增多,适应症已扩展到血液系统恶性肿瘤之外。
摘要:随着CAR-T细胞疗法的适应证不断扩大至血液系统恶性肿瘤以外的疾病,其应用日益广泛。本文回顾了现有用于预测CAR-T细胞治疗相关毒性的模型,并总结了这些模型应用中的优势与挑战。预测建模有望指导风险分层并为临床决策提供依据,但样本量较小、过拟合和数据质量欠佳,限制了模型的可重复性和广泛应用。随着CAR-T细胞疗法应用范围扩大,确定更多生物标志物、开发适用于特定情境的模型、制定针对新出现毒性的标准化指南,以及借助联邦学习促进协作式数据共享,将至关重要。 意义:整合生物标志物和临床变量的预测模型正越来越多地用于预测CAR-T细胞治疗后的潜在毒性。然而,患者群体和细胞治疗产品存在异质性、领域发展迅速,且炎症性毒性的管理方法持续进步,这些因素给CAR-T细胞治疗建模带来了重大挑战。本文全面综述了现有及新兴模型,阐述预测模型开发的关键要素,包括区分度、校准、生物标志物整合、验证和过拟合控制,并总结适用于CAR-T细胞治疗的模型优势、改进机会及未来方向。
UNLABELLED: Chimeric antigen receptor (CAR) T-cell therapy is increasingly utilized with expanding indications beyond hematologic malignancies. Here, we review existing models developed for predicting toxicities in the CAR T-cell setting and identify both strengths and challenges emerging with their application. Predictive modeling approaches offer potential to guide risk stratification and inform clinical decision-making, but small sample sizes, overfitting, and poor data quality have limited model reproducibility and widespread adoption. As utilization of CAR T-cell therapy broadens, identifying additional biomarkers, developing context-specific models, standardizing guidelines for emerging toxicities, and leveraging federated learning to promote collaborative data sharing will be critical. SIGNIFICANCE: Predictive models integrating biomarkers and clinical variables are increasingly used to forecast potential toxicities after CAR T-cell therapy. However, due to heterogeneity in patient populations and cellular therapy products, the rapidly evolving nature of the field, and continued advancements in management of inflammatory toxicities, modeling in CAR T-cell therapy faces significant challenges. This comprehensive review of existing/emerging models serves to delineate components of developing predictive models including discrimination, calibration, biomarker integration, validation, and mitigation of overfitting while highlighting strengths, opportunities for improvement, and future directions applicable to CAR T-cell therapy.
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