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基于 Alpha 型 1 极化树突状细胞的新诊断高级别神经胶质瘤疫苗接种:一项 II 期临床试验。

Alpha-type-1 Polarized Dendritic Cell-based Vaccination in Newly Diagnosed High-grade Glioma: A Phase II Clinical Trial.

机构信息

Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Division of Neurosurgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

出版信息

Anticancer Res. 2020 Nov;40(11):6473-6484. doi: 10.21873/anticanres.14669.

DOI:10.21873/anticanres.14669
PMID:33109586
Abstract

BACKGROUND/AIM: Glioblastoma multiforme (GBM) is an intractable tumor that has a very poor prognosis despite intensive treatment with temozolomide plus radiotherapy.

PATIENTS AND METHODS

Sixteen newly diagnosed patients with high-grade gliomas were enrolled in a phase II study of the α-type-1 DC vaccine. Briefly, DCs obtained from the culture of enriched monocytes in the presence of a cytokine cocktail, were pulsed with a cocktail of 5 synthetic peptides and cryopreserved until injection into patients.

RESULTS

The amount of IL-12 produced by activated DCs was higher than that previously reported. Among 15 evaluable patients, 10 showed positive CTL responses to any peptides in an ELISPOT assay. After 6 years of observation, five patients were still alive, and two of these patients were relapse-free. Moreover, a significant survival-prolonging effect was verified in DC-treated glioma patients.

CONCLUSION

Peptide-cocktail-pulsed α-type-1 DC vaccines have a potential therapeutic effect on survival when used in combination with the standard regimen, which is partly based on IL-12-IFN-γ-mediated T-cell activation.

摘要

背景/目的:尽管采用替莫唑胺联合放疗进行强化治疗,胶质母细胞瘤(GBM)仍是一种难以治疗的肿瘤,预后极差。

患者和方法

16 例新诊断的高级别胶质瘤患者入组了α-1 型 DC 疫苗的 II 期研究。简要来说,在细胞因子鸡尾酒存在的情况下,从富集的单核细胞培养物中获得的 DC 被 5 种合成肽鸡尾酒脉冲处理,并冷冻保存,直到注射给患者。

结果

激活的 DC 产生的 IL-12 量高于以前报道的水平。在 15 例可评估的患者中,10 例在 ELISPOT 检测中对任何肽均显示出阳性 CTL 反应。经过 6 年的观察,5 例患者仍然存活,其中 2 例无复发。此外,在接受 DC 治疗的脑肿瘤患者中,观察到了显著的生存延长效果。

结论

与标准方案联合使用时,肽鸡尾酒脉冲 α-1 型 DC 疫苗具有潜在的治疗效果,这部分是基于 IL-12-IFN-γ 介导的 T 细胞激活。

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