Development of therapeutic cancer vaccine

治疗性癌症疫苗的开发

• 批准号: 17016061
• 负责人: SATO Noriyuki
• 金额: $ 29.57万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17016061/
• 关键词: IAP; 滑膜肉腫; ペプチド; CTL; 癌ワクチン; 癌幹細胞; HLA class I; HDAC; HLA; HSP; 癌幹細胞抗原; テトラマー; 抗癌原; 免疫治療; HLAクラス1; 腫瘍抗原; サバイビン; SYT-SSX; ペプチド抗原; 癌ペプチドワクチン; リビン; 免疫モニタリング; HLAクラスI; エピジェネティクス

Our study clarified several new aspects of the human tumor immune response. 1) Some of IAP (inhibitors of apoptosis proteins) is considered to be candidates for human cancer vaccines. Particularly, HLA-A24 restricted peptide survivin 2B, a splicing variant of survivin gene, is immunogenic in patients with many types of cancer such as colon, pancreas, lung, oral and urogenital origins. It was indicated that patients vaccinated with this peptide could respond well as assessed by peptide-specific tetramer study. 2) The detail of the expression of HLA class I molecule in human cancers is not yet known. To this end, we developed mAb reacting on the paraffin-embeded specimen against all of HLA class I alleles. The data demonstrated that the HLA class I in more than 80 % of breast and prostate cancer was markedly decreased, and this was due to transcriptional regulation by histone deacetylation (HDAC) of the gene expression. Indeed, treatment of HLA class I down-regulated breast cancer lines with HDAC inhibitor could restore its expression on the cell surface. Currently clinical trials with survivin 2B peptide combined with HDAC inhibitor is underway in breast cancer patients. 3) We also clarified tumor antigens selectively expressing in human cancer stem cell (CSC)/cancer-initiating cell (CIC) that was sorted with side population technology. Consequently, we detected five such antigens including novel cell surface molecule. These antigens may be potential candidates for human cancer vaccines, since these are more immunogenic than non CSC/CIC antigens.

我们的研究阐明了人类肿瘤免疫反应的几个新方面。 1) 一些IAP（凋亡蛋白抑制剂）被认为是人类癌症疫苗的候选者。特别是，HLA-A24限制性肽生存素2B（生存素基因的剪接变体）在患有多种癌症（例如结肠癌、胰腺癌、肺癌、口腔癌和泌尿生殖道癌）的患者中具有免疫原性。通过肽特异性四聚体研究评估，表明接种该肽的患者可以产生良好的反应。 2)人类癌症中HLA I类分子的表达细节尚不清楚。为此，我们开发了针对石蜡包埋标本的所有 HLA I 类等位基因的 mAb。数据表明，超过 80% 的乳腺癌和前列腺癌中的 HLA I 类显着下降，这是由于组蛋白脱乙酰化 (HDAC) 对基因表达的转录调节所致。事实上，用 HDAC 抑制剂治疗 HLA I 类下调乳腺癌细胞系可以恢复其在细胞表面的表达。目前，survivin 2B 肽联合 HDAC 抑制剂的临床试验正在乳腺癌患者中进行。 3）我们还阐明了通过侧群技术分选的人类癌症干细胞（CSC）/癌症起始细胞（CIC）中选择性表达的肿瘤抗原。因此，我们检测到了五种此类抗原，包括新型细胞表面分子。这些抗原可能是人类癌症疫苗的潜在候选者，因为它们比非 CSC/CIC 抗原更具免疫原性。

项目成果

Aberrant expression and potency as a cancer immunotherapy target of alpha-methylacyl-coenzyme A racemase in prostate cancer.

• DOI: 10.1186/1479-5876-7-103
• 发表时间: 2009-12-09
• 期刊: Journal of translational medicine
• 影响因子: 7.4
• 作者: Honma I;Torigoe T;Hirohashi Y;Kitamura H;Sato E;Masumori N;Tamura Y;Tsukamoto T;Sato N
• 通讯作者: Sato N

Ptognostic impact and immunogenicity of a novel osteosarcoma antigen,papillomavirus binding factor,in patients with osteosarcoma

新型骨肉瘤抗原乳头瘤病毒结合因子对骨肉瘤患者的预后影响和免疫原性

• 发表时间: 2008
• 期刊: Cancer Sci. 99
• 作者: Tsulkahara;T.;et. al.
• 通讯作者: et. al.

Down-regulation of HLA class I antigens in prostate cancer tissues and up-regulation by histone deacetylase inhibition.

前列腺癌组织中 HLA I 类抗原的下调和组蛋白脱乙酰酶抑制的上调。

• 发表时间: 2007
• 期刊: J Urol 178
• 作者: Kitamura;H.;Sato;N.;他3名、4番目
• 通讯作者: 他3名、4番目

Biogical Heterogeneity of the Peptide-binding Motif of the 70-KDa Heat Shock Protein by Surface Plasmon Resonance Analysis

通过表面等离子共振分析 70-KDa 热休克蛋白肽结合基序的生物异质性

• 发表时间: 2007
• 期刊: Jour.Biol.Chem. 282
• 作者: Maeda;H.;et. al.
• 通讯作者: et. al.

Identification of HLA-A2- or -A24- restricted CTL epitopes possibly useful for glypican-3 -specific immunotherapy for hepatocellular carcinoma.

HLA-A2-或-A24-限制性CTL表位的鉴定可能对肝细胞癌的磷脂酰肌醇蛋白聚糖-3特异性免疫治疗有用。

• 发表时间: 2006
• 期刊: Clin. Cancer Res. 12
• 作者: Komori;H.;Sato;N.;他11名11番目
• 通讯作者: 他11名11番目