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新生抗原靶向树突状细胞疫苗在肺癌患者中诱导出具有完整分化谱的长期存活 T 细胞

英文原题:Neoantigen-targeted dendritic cell vaccination in lung cancer patients induces long-lived T cells exhibiting the full differentiation spectrum.

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Neoantigen-targeted dendritic cell vaccination in lung cancer patients induces long-lived T cells exhibiting the full differentiation spectrum.

PubMed 2024/04/15(内容时间) Cell Rep Med Q1 · IF 14(JCR 2025)

研究概要

这些数据支持该治疗在已切除的NSCLC中的可行性、安全性和免疫原性。

中文摘要

非小细胞肺癌(NSCLC)以早期切除后高复发率著称。在此,我们展示了一项I期临床试验的结果,该试验评估了一种靶向患者个体新抗原的树突状细胞(DC)疫苗在已切除NSCLC患者中的应用。在10例入组患者中,6例的疫苗制备是可行的。毒性仅限于1-2级不良事件。在6例接种疫苗的患者中,5例观察到全身性T细胞反应,且T细胞反应在接种后长达19个月仍可检测到。单细胞分析表明,有反应的T细胞群体是多克隆的,并表现出几乎全部的T细胞分化状态谱,包括初始样状态,但不包括耗竭细胞状态。在2年随访期间,6例接种疫苗的患者中有3例出现疾病复发。总体而言,这些数据支持该治疗在已切除NSCLC中的可行性、安全性和免疫原性。

展开英文摘要原文

Non-small cell lung cancer (NSCLC) is known for high relapse rates despite resection in early stages. Here, we present the results of a phase I clinical trial in which a dendritic cell (DC) vaccine targeting patient-individual neoantigens is evaluated in patients with resected NSCLC. Vaccine manufacturing is feasible in six of 10 enrolled patients. Toxicity is limited to grade 1-2 adverse events. Systemic T cell responses are observed in five out of six vaccinated patients, with T cell responses remaining detectable up to 19 months post vaccination. Single-cell analysis indicates that the responsive T cell population is polyclonal and exhibits the near-entire spectrum of T cell differentiation states, including a naive-like state, but excluding exhausted cell states. Three of six vaccinated patients experience disease recurrence during the follow-up period of 2 years. Collectively, these data support the feasibility, safety, and immunogenicity of this treatment in resected NSCLC.

论文信息

作者
Ingels J、De Cock L、Stevens D、Mayer RL、Théry F、Sanchez GS、Vermijlen D、Weening K
第一作者单位
Department of Diagnostic Sciences, Ghent University, 9000 Ghent, East-Flanders, Belgium; Cancer Research Institute Ghent (CRIG), 9000 Ghent, Easy-Flanders, Belgium.Belgium
通讯作者单位
Department of Diagnostic Sciences, Ghent University, 9000 Ghent, East-Flanders, Belgium; Cancer Research Institute Ghent (CRIG), 9000 Ghent, Easy-Flanders, Belgium; GMP Unit Cell Therapy, Ghent University Hospital, 9000 Ghent, East-Flanders, Belgium. Electronic address: bart.vandekerckhove@ugent.be.Belgium
文献类型
I 期临床试验
期刊
Cell reports. Medicine2024 May 21
原文标识
PubMed 38626769 · DOI 10.1016/j.xcrm.2024.101516