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经头颈部癌患者特洛伊疫苗诱导的 MAGE-A3 和 HPV-16 免疫。

Induction of MAGE-A3 and HPV-16 immunity by Trojan vaccines in patients with head and neck carcinoma.

机构信息

Department of Dermatology, University of Erlangen, Nuremburg, Germany.

出版信息

Head Neck. 2012 Dec;34(12):1734-46. doi: 10.1002/hed.22004. Epub 2012 Jan 27.

DOI:10.1002/hed.22004
PMID:22287423
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3725741/
Abstract

BACKGROUND

We performed a pilot study using Trojan vaccines in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). These vaccines are composed of HLA-I and HLA-II restricted melanoma antigen E (MAGE)-A3 or human papillomavirus (HPV)-16 derived peptides, joined by furin-cleavable linkers, and linked to a "penetrin" peptide sequence derived from HIV-TAT. Thirty-one patients with SCCHN were screened for the trial and 5 were enrolled.

METHODS

Enrolled patients were treated with 300 μg of Trojan peptide supplemented with Montanide and granulocyte-macrophage colony-stimulating factor (GM-CSF) at 4-week intervals for up to 4 injections.

RESULTS

Following vaccination, peripheral blood mononuclear cells (PBMCs) from 4 of 5 patients recognized both the full Trojan constructs and constituent HLA-II peptides, whereas responses to HLA-I restricted peptides were less pronounced.

CONCLUSION

This treatment regimen seems to have acceptable toxicity and elicits measurable systemic immune responses against HLA-II restricted epitopes in a subset of patients with advanced SCCHN.

摘要

背景

我们在晚期头颈部鳞状细胞癌(SCCHN)患者中使用特洛伊疫苗进行了一项试点研究。这些疫苗由 HLA-I 和 HLA-II 限制的黑色素瘤抗原 E(MAGE)-A3 或人乳头瘤病毒(HPV)-16 衍生肽组成,通过弗林切割接头连接,并与源自 HIV-TAT 的“穿透素”肽序列连接。对 31 名 SCCHN 患者进行了试验筛选,有 5 名患者入选。

方法

入选患者每 4 周接受 300μg 特洛伊肽加 Montanide 和粒细胞-巨噬细胞集落刺激因子(GM-CSF)治疗,最多 4 次注射。

结果

接种疫苗后,5 名患者中的 4 名患者的外周血单核细胞(PBMC)能够识别完整的特洛伊结构和组成的 HLA-II 肽,而对 HLA-I 限制的肽的反应则不那么明显。

结论

这种治疗方案似乎具有可接受的毒性,并在一组晚期 SCCHN 患者中引发针对 HLA-II 限制表位的可测量的全身免疫反应。

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