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

我们建立了抗血管生成的人源性单克隆抗体（MAb），并克隆了该抗体的氨基肽酶N（APN）/CD 13。APN具有潜在的肺转移能力。应用肺癌、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。建立人源性单克隆抗体后，采用Trenswell法筛选出抑制细胞运动的抗体。在识别APN/CD13的几种抗体中，MT95 - 4和MT19 - 12抗体对APN的活性有显著的抑制作用。我们报道了人抗APN单克隆抗体MT95 - 4和MT19 - 12抑制肺转移和淋巴结转移。1）在静脉内转移模型中，接受抗APN抗体MT95 - 4的小鼠的肺肿瘤数目减少（96.7 ± 14.3对22.5 ± 13.1，p <0.001）。2)在原位植入模型中，抗APN抗体MT95 - 4处理的肿瘤和对照PBS肿瘤之间没有显著差异（211.1 ± 31.1mm 3对204.4 ± 32.1 = 3）。3)与定性观察结果一致，接受抗APN抗体MT95 - 4的小鼠的淋巴结重量降低（475.6 ± 94.2mg vs 116.7 ± 25.9mg，p <0.001）。糖链的改变导致了这些变化，因此目前正在研究哪些糖链的改变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。这种抑制淋巴结转移的方法可应用于癌症的临床治疗，特别是在放射治疗中预防转移。

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.