Cancer Peptide Vaccine Therapy Developed from Oncoantigens Identified through Genome-wide Expression Profile Analysis for Bladder Cancer
Cancer Peptide Vaccine Therapy Developed from Oncoantigens Identified through Genome-wide Expression Profile Analysis for Bladder Cancer
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DOI：
10.1093/jjco/hys069
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发表时间：
2012-07-01
影响因子：
2.4
通讯作者：
Fujioka, Tomoaki
中科院分区：
文献类型：
--
作者：
Obara, Wataru;Ohsawa, Ryuji;Fujioka, Tomoaki
癌症疫苗治疗领域目前有望成为继手术、化疗、放射治疗之后癌症治疗的第四选择。通过全基因组表达谱分析，我们开发了一种新型的膀胱癌多肽疫苗疗法。在众多在癌细胞中反式激活的癌蛋白中，我们重点关注了M期磷酸蛋白1和含有1的DEP结构域，这两种抗原都是在膀胱癌细胞生长中起关键作用的癌症-睾丸抗原，作为膀胱癌药物开发的候选分子。为了从这些肿瘤抗原中识别多肽表位，我们用这些多肽对晚期膀胱癌患者进行了临床试验，我们鉴定了对应于M期磷酸蛋白1和DEP结构域的部分人类白细胞抗原A24限制性多肽表位，这些表位可以诱导多肽特异性细胞毒性T淋巴细胞。利用这些多肽，我们发现含有1-衍生肽疫苗的M期磷酸蛋白1和DEP结构域具有良好的耐受性，没有任何严重的不良反应，并能在体内有效地诱导多肽特异性细胞毒性T淋巴细胞。多肽疫苗治疗膀胱癌的新途径被认为是一种有前途的治疗方法。
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.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.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.The novel approach adopted in the treatment with peptide vaccines is considered to be a promising therapy for bladder cancer.