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:Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Melanoma: A Systematic Review of Phase One Clinical Trials.
Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Melanoma: A Systematic Review of Phase One Clinical Trials.
最终分析并讨论了 5 项研究,共纳入 15 例接受 CAR-T 细胞治疗的黑色素瘤患者。
引言:黑色素瘤日益成为健康问题,全球发病率逐年上升,但难治性疾病的治疗选择有限。嵌合抗原受体(CAR)T细胞疗法在血液系统恶性肿瘤中取得良好结果,但其用于黑色素瘤等实体癌的价值尚未确立。我们系统综述I期试验,以评估并描述CAR-T细胞疗法治疗黑色素瘤的基础安全性和疗效认识。 方法:本系统综述依据Cochrane干预措施系统综述手册及系统综述和荟萃分析优先报告条目(PRISMA)指南开展。检索截至2025年11月18日发表、报告CAR-T细胞疗法治疗黑色素瘤患者结果的文献,并汇总和分析研究、患者及治疗特征。 结果:共筛查2726篇文献,最终纳入并讨论5项研究,共15例接受CAR-T细胞治疗的黑色素瘤患者。所有T细胞疗法均为自体治疗,CAR靶点包括GD2、PD-1和cMET,细胞剂量差异较大。汇总数据中临床应答不一,部分患者获得部分或完全临床应答。治疗相关反应为1级或2级,未报告严重不良事件,包括神经毒性,也未见因治疗相关毒性而限制治疗或导致死亡的事件。CAR-T细胞扩增峰值通常出现在第7至28天,但各研究中细胞持久性有限。 结论:CAR-T细胞疗法是处于早期阶段的黑色素瘤新型治疗方法。结果仍属初步,且主要为描述性发现,受到研究异质性和样本量小的限制。仍需开展更多I期试验及后续II/III期试验,进一步明确其直接临床可行性。
Introduction Melanoma is a growing health concern, with global incidence increasing annually. However, treatment for refractory disease is currently limited. Chimeric antigen receptor (CAR) T-cell therapy has shown promising results in haematological malignancies. Despite this, its utility in solid cancers, such as melanoma, is not yet established. We performed a systematic review of phase one trials to help determine and describe foundational understandings of the safety and efficacy of CAR T-cell therapy for melanoma.MethodsThis systematic review was conducted in accordance with the Cochrane Collaboration Handbook for Systematic Review of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement Guidelines. Databases were searched to identify articles before November 18, 2025, which described the use of CAR T-cell therapy in melanoma patients with published results. Study, patient, and treatment characteristics were summarised and analysed.ResultsIn total, 2726 articles were screened. Ultimately 5 studies comprising 15 patients with melanoma treated with CAR T-cell therapy were analysed and discussed. T-cell therapies were all autologous and the targets for the CAR T-cell therapies included GD2, PD-1 and cMET antigens across a wide variety of cell doses. Across pooled data, clinical responses varied, with some patients displaying either a partial or complete clinical response. Treatment related effects were of grade one or two severity, with no serious adverse effects reported, including neurotoxicity side effects, or treatment limited related toxicity/mortality events. Peak expansion typically occurred within day 7 to 28, but persistence was limited across studies.ConclusionCAR T-cell therapy for melanoma is a novel treatment approach in its infancy. Results are preliminary, and remain largely descriptive, as findings are limited by heterogeneity and small sample sizes. Further investigation through additional phase one trials, and subsequent phase two/three trials, are required for better establishing direct clinical viability.
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