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:Biomarkers for predicting CAR-T cell therapy outcomes in B-cell acute lymphoblastic leukemia: a systematic review.
Biomarkers for predicting CAR-T cell therapy outcomes in B-cell acute lymphoblastic leukemia: a systematic review.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
尽管已有一些有前景的见解,但毒性分级系统的异质性、生物标志物阈值的不一致以及回顾性研究设计限制了临床标准化。未来方向强调减瘤桥接治疗、生物标志物指导的组合策略(例如针对 TP53 突变的 MDM2 抑制剂),以及整合预测模型的多中心验证,以优化个性化 CAR-T 治疗策略。
嵌合抗原受体(CAR)T细胞疗法已经彻底改变了复发/难治性B细胞急性淋巴细胞白血病(B-ALL)的治疗,但细胞因子释放综合征(CRS)、神经毒性(ICANS)以及长期疗效可变等挑战仍然存在。本系统综述评估了生物标志物在预测CAR-T 治疗结局、毒性风险以及指导个体化治疗策略中的作用。
遵循PRISMA指南,我们系统检索了PubMed、Web of Science和Embase中2018-2024年发表的研究。共纳入33项研究,涉及2,095例患者进行分析。
关键发现确定了肿瘤负荷和微小残留病(MRD)作为双重预测性生物标志物。高肿瘤负荷(原始细胞≥40%)与完全缓解率降低(87% vs. 100%)及CRS/ICANS风险增加相关,而MRD阴性(NGS阈值<10⁻⁶)预测更优的2年无事件生存率(68% vs. 23%)。CAR-T 功能参数,包括PD-1/LAG-3表达(CD4+细胞中>5.2%)和峰值扩增动力学,将疗效与毒性权衡相关联。遗传生物标志物(IKZF1突变、复杂核型)和生化指标(m-EASIX >6.2、铁蛋白≥10,000 ng/mL)进一步分层风险。单向疗效生物标志物包括T细胞亚群(如CD8+初始T细胞)和B细胞再生障碍,而IL-6动态特异性预测CRS严重程度。
Following PRISMA guidelines, we systematically searched PubMed, Web of Science, and Embase for studies published between 2018-2024. A total of 33 studies involving 2,095 patients were included in the analysis.
Key findings identified tumor burden and minimal residual disease (MRD) as dual-predictive biomarkers. High tumor burden ( 40% blasts) correlated with reduced complete remission rates (87% vs. 100%) and increased CRS/ICANS risks, while MRD negativity (NGS threshold <10 ) predicted superior 2-year event-free survival (68% vs. 23%). CAR-T functional parameters, including PD-1/LAG-3 expression (>5.2% in CD4+ cells) and peak expansion kinetics, linked efficacy to toxicity trade-offs. Genetic biomarkers (IKZF1 mutations, complex karyotypes) and biochemical indicators (m-EASIX >6.2, ferritin 10,000 ng/mL) further stratified risks. Unidirectional efficacy biomarkers included T-cell subsets (e.g., CD8+ naive T cells) and B-cell aplasia, while IL-6 dynamics specifically predicted CRS severity. DISCUSSION: Despite promising insights, heterogeneity in toxicity grading systems, inconsistent biomarker thresholds, and retrospective study designs limit clinical standardization. Future directions emphasize cytoreductive bridging therapies, biomarker-guided combinatorial approaches (e.g., MDM2 inhibitors for TP53 mutations), and multicenter validation of integrated predictive models to optimize personalized CAR-T therapy strategies.
在 PubMed 查看 → 出版商原文(DOI) 全文 PDF(PMC)· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
MEMBER ACCOUNT
登录成功会直接打开下一页。