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PSF1 来源的可溶性 HLA 相关肽具有癌症疫苗效力。

Soluble HLA-associated peptide from PSF1 has a cancer vaccine potency.

机构信息

Biomarker R&D Department, Shionogi & Co., Ltd, Osaka, 561-0825, Japan.

Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Osaka, 561-0825, Japan.

出版信息

Sci Rep. 2017 Sep 11;7(1):11137. doi: 10.1038/s41598-017-11605-2.

Abstract

Partner of sld five 1 (PSF1) is an evolutionary conserved DNA replication factor involved in DNA replication in lower species, which is strongly expressed in normal stem cell populations and progenitor cell populations. Recently, we have investigated PSF1 functions in cancer cells and found that PSF1 plays a significant role in tumour growth. These findings provide initial evidence for the potential of PSF1 as a therapeutic target. Here, we reveal that PSF1 contains an immunogenic epitope suitable for an antitumour vaccine. We analysed PSF1 peptides eluted from affinity-purified human leukocyte antigen (HLA) by mass spectrometry and identified PSF1 peptide (YLYDRLLRI) that has the highest prediction score using an in silico algorithm. PSF1 peptide induced PSF1-specific cytotoxic T lymphocyte responses such as the production of interferon-γ and cytotoxicity. Because PSF1 is expressed in cancer cell populations and highly expressed in cancer stem cell populations, these data suggest that vaccination with PSF1 peptide may be a novel therapeutic strategy for cancer treatment.

摘要

sld five 1(PSF1)的伴侣是一种进化上保守的 DNA 复制因子,参与较低物种的 DNA 复制,在正常干细胞群体和祖细胞群体中强烈表达。最近,我们研究了 PSF1 在癌细胞中的功能,发现 PSF1 在肿瘤生长中起着重要作用。这些发现为 PSF1 作为治疗靶点的潜力提供了初步证据。在这里,我们揭示 PSF1 含有一个适合抗肿瘤疫苗的免疫原性表位。我们通过质谱法分析了从亲和纯化的人类白细胞抗原(HLA)中洗脱的 PSF1 肽,并使用计算机算法鉴定了 PSF1 肽(YLYDRLLRI),其预测评分最高。PSF1 肽诱导 PSF1 特异性细胞毒性 T 淋巴细胞反应,如干扰素-γ的产生和细胞毒性。由于 PSF1 在癌细胞群体中表达,并且在癌症干细胞群体中高度表达,这些数据表明用 PSF1 肽进行疫苗接种可能是癌症治疗的一种新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2736/5593935/e27041cafd92/41598_2017_11605_Fig1_HTML.jpg

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