Development for new cancer vaccine against heterogenicity and HLA-loss of tumor

开发针对肿瘤异质性和 HLA 缺失的新型癌症疫苗

• 批准号: 16591297
• 负责人: TSUNODA Takuya
• 金额: $ 2.18万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591297/
• 关键词: Epitope peptide; Tumor heterogenicity; HLA Loss; CTL; Cancer vaccine; ペプチド; 細胞障害性T細胞; 免疫療法; がんワクチン療法

Recently, cancer vaccine using epitope peptides was performed all over the world. Epitope peptides induced the strong cytotoxic T lymphocytes (CTL) in cancer patients, therefore clinical trials of cancer vaccine were performed. However, the outcome of clinical trial has not so excellent. One of the reasons was due to the heterogenicity and HLA-loss of the tumor. To overcome these problems, we focused on the tumor angiogenesis and examined the immunogenicity for tumor-angiogenesis related targets.In this study, we have determined the immunogenicity from these targets. We have determined epitope peptides restricted to HLA-A^*2402 which was the most common in Japanese. These findings may suggest that tumor-angiogenesis related targets are excellent targets to improve the clinical efficacy of cancer vaccine.

近年来，利用表位多肽研制的肿瘤疫苗在世界范围内得到了广泛的应用。表位多肽可诱导肿瘤患者体内产生较强的细胞毒性T淋巴细胞(CTL)，因此开展了肿瘤疫苗的临床试验。然而，临床试验的结果并不是那么好。其中一个原因是肿瘤的异质性和人类白细胞抗原的缺失。为了克服这些问题，我们聚焦于肿瘤血管生成，检测了肿瘤血管生成相关靶点的免疫原性。在本研究中，我们确定了这些靶点的免疫原性。我们已经确定了日本人最常见的人类白细胞抗原-A^*2402的表位多肽。这些发现可能表明，肿瘤血管生成相关靶点是提高肿瘤疫苗临床疗效的极佳靶点。

项目成果

Dendritic cell might be one of key factors for eliciting antitumor effect by chemo-immunotherapy in vivo.

树突状细胞可能是体内化学免疫疗法引发抗肿瘤作用的关键因素之一。

• 发表时间: 2005
• 期刊: Cancer Immunology Immunotherapy 54
• 作者: Mushiake H;Tsunoda T;Nukatsuka M;Shimao K;Fukushima M;Tahara H.
• 通讯作者: Tahara H.

Rationale for anti-angiogenic cancer therapy with vaccination using epitope peptides derived from human vascular endothelial growth factor receptor 2 (VEGFR2).

使用源自人血管内皮生长因子受体 2 (VEGFR2) 的表位肽进行疫苗接种进行抗血管生成癌症治疗的基本原理。

• 发表时间: 2005
• 期刊: Cancer Research 65
• 作者: Wada S;Tsunoda T;et al.
• 通讯作者: et al.

Enhancement of cytotoxic T-lymphocyte responses in patients with gastrointestinal malignancies following vaccination with CEA peptide-pulsed dendritic cells

• DOI: 10.1007/s00262-003-0491-7
• 发表时间: 2004-07-01
• 期刊: CANCER IMMUNOLOGY IMMUNOTHERAPY
• 影响因子: 5.8
• 作者: Matsuda, K;Tsunoda, T;Yamaue, H
• 通讯作者: Yamaue, H

Identification of immunoglobulin superfamily 11 (IGSF11) as a novel target for cancer immunotherapy of gastrointestinal and hepatocellular carcinomas

• DOI: 10.1111/j.1349-7006.2005.00073.x
• 发表时间: 2005-08-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Watanabe, T;Suda, T;Nakamura, Y
• 通讯作者: Nakamura, Y

Effect of imatinib (STI571) on metastatic gastrointestinal stromal tumors : report of a case.

伊马替尼（STI571）对转移性胃肠道间质瘤的影响：一例报告。

• 发表时间: 2005
• 期刊: Surg Today. 35
• 作者: Yuichi Ando;Takuya Tsunoda;et al.
• 通讯作者: et al.