为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Efficacy and Safety of Cellular Immunotherapy by Local Infusion for Liver Tumor: A Systematic Review and Meta-Analysis.
Efficacy and Safety of Cellular Immunotherapy by Local Infusion for Liver Tumor: A Systematic Review and Meta-Analysis.
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通过局部灌注的免疫细胞疗法对肝癌患者有效,毒性可控。与微创治疗联合应用时显示出更好的预后。考虑到潜在的局限性,需要更多随机对照试验为我们的发现提供确凿证据。
细胞免疫治疗已成为肝肿瘤患者一种有前景的新疗法。然而,由于大多数免疫细胞通过静脉注射递送,其效果有限,且可能产生全身毒性。本研究的目的是探讨局部输注细胞免疫治疗的疗效和安全性,这似乎是一种有前景的方法,但目前尚未得到充分研究。
检索了PubMed、Web of Science、Embase和Cochrane Library数据库以获取文献。研究总缓解率(ORR)、总生存期(OS)率和不良事件,以评估局部区域治疗的有效性和安全性。采用非随机研究方法学指数(MINORS)评分评估文章的方法学质量。使用Stata 15.0进行meta分析。
共纳入17项符合条件的研究,涉及318例患者。随机效应模型显示,局部细胞输注治疗的ORR为48%(95% CI:26%-70%)。汇总OS率在6个月时为94%(95% CI:83%-100%),12个月时为87%(95% CI:74%-96%),24个月时为42%(95% CI:16%-70%)。亚组分析提示,微创治疗和无转移与更好的ORR显著相关。14项研究报告了与局部灌注细胞治疗相关的多种不良事件。免疫细胞区域输注后最常见的并发症为骨髓抑制(66%)、发热(50%)、胃肠道毒性(22%)、肝功能障碍(15%)以及胸腔积液和/或腹水(14%)。
Cellular immunotherapy has become a new and promising treatment for patients with liver tumor. However, as most immune cells are delivered by intravenous injection, the effect is limited and is likely to produce systemic toxicity. Here, the objective was to investigate the efficacy and safety of cellular immunotherapy by local infusion, which seems to be a promising approach and has not been well-studied.
The PubMed, Web of Science, Embase, and Cochrane Library databases were searched to obtain literature. The overall response rate (ORR), overall survival (OS) rates, and adverse events were investigated to evaluate the effectiveness and safety of locoregional therapy. The methodological quality of the articles was assessed using the methodological index for non-randomized studies (MINORS) score. The meta-analysis was performed using Stata 15.0.
The eligible 17 studies involved a total of 318 patients. The random-effects model demonstrated that the ORR of local cell infusion therapy was 48% (95% confidence interval [CI]: 26%-70%). The pooled OS rate was 94% (95% CI: 83%-100%) at 6 months, 87% (95% CI: 74%-96%) at 12 months, and 42% (95% CI: 16%-70%) at 24 months. Subgroup analyses suggested that minimally invasive treatment and absence of metastasis were significantly associated with better ORR. Fourteen studies reported a variety of adverse events related to cell therapy by local perfusion. The most common complications after regional infusion of immune cells were myelosuppression (66%), fever (50%), gastrointestinal toxicity (22%), hepatic dysfunction (15%), and pleural effusion and/or ascites (14%).
Immune cell therapy through local perfusion is effective for patients with liver cancer, with manageable toxicity. It demonstrates better prognosis when combined with minimally invasive therapy. Considering the potential limitations, more randomized controlled trials are needed to provide solid evidence for our findings.
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