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基于膀胱癌全基因组表达谱分析鉴定的肿瘤相关抗原研制的癌症肽疫苗治疗。

Cancer peptide vaccine therapy developed from oncoantigens identified through genome-wide expression profile analysis for bladder cancer.

机构信息

Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka 020-8505, Japan.

出版信息

Jpn J Clin Oncol. 2012 Jul;42(7):591-600. doi: 10.1093/jjco/hys069. Epub 2012 May 25.

Abstract

OBJECTIVE

The field of cancer vaccine therapy is currently expected to become the fourth option in the treatment of cancer after surgery, chemotherapy and radiation therapy. We developed a novel cancer peptide vaccine therapy for bladder cancer through a genome-wide expression profile analysis.

METHODS

Among a number of oncoproteins that are transactivated in cancer cells, we focused on M phase phosphoprotein 1 and DEP domain containing 1, both of which are cancer-testis antigens playing critical roles in the growth of bladder cancer cells, as candidate molecules for the development of drugs for bladder cancer. In an attempt to identify the peptide epitope from these oncoantigens, we conducted a clinical trial using these peptides for patients with advanced bladder cancer.

RESULTS

We identified HLA-A24-restricted peptide epitopes corresponding to parts of M phase phosphoprotein 1 and DEP domain containing 1 proteins, which could induce peptide-specific cytotoxic T lymphocytes. Using these peptides, we found that M phase phosphoprotein 1- and DEP domain containing 1-derived peptide vaccines could be well tolerated without any serious adverse events, and effectively induced peptide-specific cytotoxic T lymphocytes in vivo.

CONCLUSIONS

The novel approach adopted in the treatment with peptide vaccines is considered to be a promising therapy for bladder cancer.

摘要

目的

癌症疫苗疗法领域目前有望成为继手术、化疗和放疗之后癌症治疗的第四种选择。我们通过全基因组表达谱分析开发了一种新型膀胱癌癌症肽疫苗疗法。

方法

在癌细胞中转录激活的许多癌蛋白中,我们将重点放在有丝分裂期磷酸蛋白 1 和 DEP 结构域包含蛋白 1 上,这两种蛋白都是在膀胱癌细胞生长中起关键作用的癌症睾丸抗原,是开发膀胱癌药物的候选分子。为了从这些肿瘤抗原中鉴定出肽表位,我们针对晚期膀胱癌患者进行了一项使用这些肽的临床试验。

结果

我们鉴定出与有丝分裂期磷酸蛋白 1 和 DEP 结构域包含蛋白 1 部分相对应的 HLA-A24 限制性肽表位,这些肽表位能够诱导肽特异性细胞毒性 T 淋巴细胞。使用这些肽,我们发现有丝分裂期磷酸蛋白 1 和 DEP 结构域包含 1 衍生肽疫苗具有良好的耐受性,没有任何严重的不良事件,并且能够有效地在体内诱导肽特异性细胞毒性 T 淋巴细胞。

结论

该研究采用的肽疫苗治疗方法被认为是一种有前途的膀胱癌治疗方法。

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