Clinical appliance to patients with lung cancer by human monoclonal antibody recognized Aminopeptidase N.

氨肽酶N识别的人单克隆抗体在肺癌患者中的临床应用。

• 批准号: 18591571
• 负责人: MASAYUKI Miyake
• 金额: $ 2.49万
• 依托单位: Tazuke Kofukai Medical Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591571/
• 关键词: Aminomotidase N; CD13; Angiogenesis; Human Monoclonal Antibody; Metastasis Inhibition; アミノペプチダーゼN

We established the human type monoclonal antibody (MAb) suppressing angiogenesis and the cloning of this antibody reveals Aminopeptidase N (APN)/CD13. The APN gained a potential ability of metastasis to the lung. Using the actual clinical specimens of lung cancer, colon cancer and pancreatic cancer, we found that the expression of APN had an association with angiogenesis, and was a significant factor of poor prognosis. After establishment in human type monoclonal antibody, we used assay of Trenswell and sorted the antibody that inhibited cell motility. In particular, MT95-4 and MT19-12 antibody significantly inhibited activity of APN among several kinds of antibody that recognized APN/CD13. We reported that human anti-APN monoclonal antibody MT95-4 and MT19-12 suppressed metastases to lung and lymph node. l)The number of lung tumors was reduced in mice that received anti APN antibody MT95-4 in intravenously metastatic model (96.7±14.3 vs 22.5±13.1, p<0.001). 2) There was no significant difference between Anti APN antibody MT95-4 treated tumors and control PBS tumors in orthotopically implantation model (211.1±31.1mm3 vs 204.4±32.1=3). 3) Consistent with qualitative observations, the lymph node weights were reduced in mice that received anti APN antibody MT95-4 (475.6, ±94.2mg vs 116.7±25.9mg, p<0.001). The modification of the sugar chain resulted in such changes, thus currently it is studied which kinds of sugar chain changes might associate with the tumor metastasis. The function of effect has been unclear yet, but there are relationships between the modification of the sugar chain and Angiogenesis. This modality to suppress lymphatic metastasis could be applied to clinical therapy of cancers, especially for the prevention of metastasis during radiotherapy.

我们建立了抑制血管生成的人型单抗，并克隆了氨基肽酶N(APN)/CD13。APN获得了潜在的肺转移能力。利用肺癌、结肠癌和胰腺癌的实际临床标本，我们发现APN的表达与血管生成有关，是预后不良的重要因素。建立人型单抗后，采用Trenswell法对抑制细胞运动的抗体进行分选。在识别APN/CD13的几种抗体中，MT95-4和MT19-12抗体对APN的活性有明显的抑制作用。我们报道了人抗APN单抗MT95-4和MT19-12对肺和淋巴结转移的抑制作用。(L)在静脉转移模型中，接受抗APN抗体的小鼠肺肿瘤数量减少(96.7士14.3vs22.5士13.1p&lt；0.001)。2)在原位种植模型中，抗APN抗体MT95-4治疗组与对照组相比差异无统计学意义(211.1±31.1 mm~3 vs 204.4±32.1±3)mm~3。3)与定性观察一致，给予抗APN抗体的小鼠淋巴结重量减轻(475.6，±94.2 mg vs 116.7±25.9 mg，p&lt；0.001)。糖链的修饰导致了这种变化，因此目前研究哪种糖链的变化可能与肿瘤转移有关。其作用机制尚不清楚，但糖链的修饰与血管生成之间存在一定的关系。这种抑制淋巴转移的方法可以应用于肿瘤的临床治疗，特别是预防放疗过程中的转移。

项目成果

Clinicopathological significance of Aminopeptidase N/CD13 expression in human gastric carcinoma.

人胃癌中氨基肽酶 N/CD13 表达的临床病理意义。

• 发表时间: 2005
• 期刊: Hepato-gastroenterol. (in press)
• 作者: Kawamura;J. et al.
• 通讯作者: J. et al.

Hypoxia and hypoxia-inducible factor-1 expression enhance osteolytic bone 2007 metastases of breast cancer.

缺氧和缺氧诱导因子 1 表达增强乳腺癌的溶骨性骨 2007 转移。

• 发表时间: 2007
• 期刊: Cancer Res. 67
• 作者: Hiraga T.;et. al.
• 通讯作者: et. al.

Suppression of metastasis by Human-type Monoclonal Antibody recognizing Aminopeptidase N. (Abstract #4854)

识别氨基肽酶 N 的人型单克隆抗体对转移的抑制（摘要）

• 发表时间: 2007
• 作者: Tokuhara,T.;et. al.
• 通讯作者: et. al.

Gallate, the component of HIF-inducing catechins, inhibits HIF prolyl hydroxylase.

• DOI: 10.1016/j.bbrc.2006.10.025
• 发表时间: 2006-12
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: F. Tsukiyama;Y. Nakai;Masataka Yoshida;T. Tokuhara;K. Hirota;Akiko Sakai;H. Hayashi;T. Katsumata

EGFR mutations in patients with brain metastases from lung cancer:: Association with the efficacy of gefitinib

• DOI: 10.1215/15228517-2005-002
• 发表时间: 2006-04-01
• 期刊: NEURO-ONCOLOGY
• 影响因子: 15.9
• 作者: Shimato, S;Mitsudomi, T;Yoshida, J
• 通讯作者: Yoshida, J