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:Chimeric antigen receptor modified T cells directed against CD19 (CTL019) in patients with relapsed, refractory CLL: a systematic review and meta-analysis.
Chimeric antigen receptor modified T cells directed against CD19 (CTL019) in patients with relapsed, refractory CLL: a systematic review and meta-analysis.
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这项荟萃分析提示,与低剂量治疗相比,高剂量 CART-19 与 CLL 患者更高的缓解率和更好的生存结局相关。
慢性淋巴细胞白血病(CLL)是一种血液系统恶性肿瘤,特征为骨髓中淋巴细胞过量生成。CLL新兴治疗策略之一是嵌合抗原受体(CAR)T细胞疗法,即通过基因修饰使T细胞更有效识别和靶向癌细胞。本研究旨在系统比较靶向CD19的CAR-T 细胞(CART-19)高剂量与低剂量治疗复发/难治性CLL患者的疗效。
为鉴定相关研究,我们全面检索PubMed、Scopus和Web of Science数据库,检索截至2023年4月。主要结局包括完全缓解(CR)和部分缓解(PR)等治疗缓解率,以及细胞因子释放综合征(CRS)发生率所指示的毒性。此外,还开展敏感性和偏倚分析,以评估结果的稳健性。
共有4项随机对照试验(RCT),纳入89例复发/难治性CLL患者,符合纳入标准。比较高剂量与低剂量CART-19疗法的缓解率后发现,高剂量组CR和PR率显著更高(标准化均数差[SMD],95%置信区间[CI]:1.02[0.10,1.94];P<0.05)。然而,CTL019剂量与CRS发生率之间无显著关联(P>0.05)。
本荟萃分析提示,与低剂量疗法相比,高剂量CART-19与CLL患者缓解率和生存结局改善相关。然而,由于研究结果存在差异,仍需开展更大规模、设计良好的试验,以确定CLL CART-19疗法的最佳剂量策略。
Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by the excessive production of lymphocytes in the bone marrow. One of the emerging therapeutic strategies for CLL is chimeric antigen receptor (CAR) T-cell therapy, wherein T-cells are genetically modified to recognize and target cancer cells more effectively. The present study aims to systematically compare the therapeutic impact of high-dose versus low-dose status of CAR T-cell therapy targeting CD19 (CART-19) in patients with relapsed or refractory CLL.
To identify relevant studies, a comprehensive literature search was conducted in PubMed, Scopus, and Web of Science databases up to April 2023. The primary outcome measures included treatment response rates, assessed as complete response (CR) and partial response (PR), and toxicity, as indicated by the incidence of cytokine release syndrome (CRS). Additionally, sensitivity and bias analyses were performed to evaluate the robustness of the findings.
Four randomized controlled trials (RCTs) comprising 89 patients with relapsed or refractory CLL met the inclusion criteria. Comparison of treatment response rates between high-dose and low-dose CART-19 therapy demonstrated a significantly higher complete and partial response rate in the high-dose group (SMD [95% CI]: 1.02 [0.10, 1.94]; P<0.05). However, no significant association was observed between CTL019 dosage and the incidence of CRS (P>0.05).
This meta-analysis suggests that high-dose CART-19 is associated with improved response rates and survival outcomes in patients with CLL compared to low-dose therapy. However, due to variability in study results, further large-scale, well-designed trials are required to establish the optimal therapeutic dosing strategy for CART-19 therapy in CLL.
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