Creation of a novel therapeutic antibody for tumor metastasis-Targeting Tumor Vasculogenic Mimicry-

开发新型肿瘤转移治疗抗体-靶向肿瘤血管生成拟态-

• 批准号: 22890192
• 负责人: NOMURA Tetsuya
• 金额: $ 2.01万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22890192/
• 关键词: 転移; 腫瘍擬似血管; ファージ表面提示法; 免疫抗体ライブラリ; がん転移; 免疫ファージ抗体ライブラリ; 一本鎖抗体; パンニング

In this study, we had an attempt to develop a novel therapy for tumor. Recent years, it is reported that in the tumor tissue tumor cells compose luminal structure as like vessel. This structure is called as tumor vasculogenic mimicry(TVM). There are many red blood cells in a part of TVM. It is expected that TVM has an important role to metastasize via blood flow. Therefore, it expects that the inhibition of both angiogenesis and TVM can result in the inhibition of tumor growth and metastasis. Therefore, we had an attempt to create anti-TVM antibody for tumor therapy, using phage-display technique. Next, we evaluated tumor growth suppressive effect by TVM vaccine therapy for tumor bearing mice to clarify how TVM development associates with metastasis. As the result, in TVM-immune mice, tumor growth had a tendency to be suppressed, compared with non-treated mice. In addition, to evaluate TVM property as blood vessel, we measured enzyme activity which has high activity in endothelial cell. As the result, in TVM, we can't confirm the elevated activity. Thus, we clarified that TVM possess properties differing from blood vessel in spite of being similar in structure to them.

本研究试图开发一种新的肿瘤治疗方法。近年来，有报道称肿瘤组织中肿瘤细胞组成类似血管的管腔结构。这种结构被称为肿瘤血管生成拟态（TVM）。在TVM的一部分中有许多红细胞。预期TVM在通过血流转移中具有重要作用。因此，预期抑制血管生成和TVM两者可导致抑制肿瘤生长和转移。因此，我们尝试利用噬菌体展示技术制备抗TVM抗体用于肿瘤治疗。接下来，我们评估了TVM疫苗治疗对荷瘤小鼠的肿瘤生长抑制作用，以阐明TVM发展与转移的关系。结果，与未治疗的小鼠相比，在TVM免疫小鼠中，肿瘤生长有被抑制的趋势。此外，为了评价TVM作为血管的性质，我们测量了在内皮细胞中具有高活性的酶活性。因此，在TVM中，我们无法确认升高的活性。因此，我们阐明了TVM具有不同于血管的性质，尽管在结构上与它们相似。

项目成果

Arsenic trioxide induces down-regulation of gp46 via protein oxidation : proteomics analysis of oxidative modified proteins in As2O3-treated HTLV-1-infected cells.

三氧化二砷通过蛋白质氧化诱导 gp46 下调：As2O3 处理的 HTLV-1 感染细胞中氧化修饰蛋白质的蛋白质组学分析。

• 发表时间: 2010
• 期刊: Pharmazie
• 影响因子: 1.6
• 作者: Nabeshi H.;Kamada H.;et al.
• 通讯作者: et al.

DDS技術を駆使した腫瘍組織血管標的がん免疫療法の開発

利用DDS技术开发针对肿瘤组织和血管的癌症免疫疗法

• 发表时间: 2011
• 期刊: Drug Delivery System
• 作者: 田所由利子;江藤宏美;片岡弥恵子;八重ゆかり;浅井宏美;飯田真理子;櫻井綾香;堀内成子;根橋佳奈;澤田啓介;厚味厳一;野村鉄也
• 通讯作者: 野村鉄也

トランスフェリンリポソームによる細胞内送達とがん治療への応用

使用转铁蛋白脂质体进行细胞内递送及其在癌症治疗中的应用

• 发表时间: 2011
• 期刊: 人工血液
• 作者: Nomura T;Abe Y;Kamada H;Shibata H;Kayamuro H;Inoue M;Kawara T;Arita S;Furuya T;Yamashita T;Nagano K;Yoshikawa T;Yoshioka Y;Mukai Y;Nakagawa S;Taniai M;Ohta T;Serada S;Naka T;Tsunoda SI;Tsutsumi Y;平田圭一
• 通讯作者: 平田圭一

Vaccination with tumor endothelial cells isolated from solid tumor inhibits tumor growth and angiogenesis

使用从实体瘤中分离的肿瘤内皮细胞进行疫苗接种可抑制肿瘤生长和血管生成

• 发表时间: 2011
• 作者: Kayamuro H;Yoshioka Y;Abe Y;Arita S;Katayama K;Nomura T;Yoshikawa T;Kubota-Koketsu R;Ikuta K;Okamoto S;Mori Y;Kunisawa J;Kiyono H;Itoh N;Nagano K;Kamada H;Tsutsumi Y;Tsunoda S;Nomura T
• 通讯作者: Nomura T

Interleukin-1 Family Cytokines as Mucosal Vaccine Adjuvants for Induction of Protective Immunity against Influenza Virus

• DOI: 10.1128/jvi.01182-10
• 发表时间: 2010-12-01
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Kayamuro, Hiroyuki;Yoshioka, Yasuo;Tsunoda, Shin-Ichi
• 通讯作者: Tsunoda, Shin-Ichi