公开(公告)号：US6113897A

公开(公告)日：2000-09-05

申请号：US580166

申请日：1995-12-28

申请人： Keld Dan.o slashed. ,  Ebbe R.o slashed.nne ,  Niels Behrendt ,  Vincent Ellis ,  Gunilla H.o slashed.yer-Hansen ,  Charles Pyke ,  Nils Bruenner

发明人： Keld Dan.o slashed. ,  Ebbe R.o slashed.nne ,  Niels Behrendt ,  Vincent Ellis ,  Gunilla H.o slashed.yer-Hansen ,  Charles Pyke ,  Nils Bruenner

IPC分类号： A61K38/00 ,  A61K38/18 ,  A61K38/49 ,  A61K38/55 ,  A61K39/395 ,  C07K14/705 ,  C07K16/28 ,  C12N9/72 ,  C12N15/12 ,  C12Q1/68 ,  G01N33/50 ,  G01N33/574 ,  G01N33/86 ,  A61K51/00 ,  C12N9/68 ,  G01N33/53

CPC分类号： C07K14/705 ,  A61K39/3955 ,  C07K16/28 ,  C07K16/2896 ,  C12N9/6462 ,  C12Q1/6886 ,  C12Y304/21073 ,  G01N33/5011 ,  G01N33/57446 ,  G01N33/86 ,  C07K2317/76 ,  C07K2317/77 ,  G01N2333/9723

摘要： A monoclonal or polyclonal antibody directed against urokinase plasminogen activator receptor (u-PAR), or a subsequence, analogue or glycosylation variant thereof. Antibodies are disclosed which react with free u-PAR or with complexes between u-PA and u-PAR and which are capable of 1) catching u-PAR in ELISA, or 2) detecting u-PAR, e.g. in blotting, or 3) in radioimmunoprecipitation assay precipitate purified u-PAR in intact or fragment form, or 4) is useful for immunohistochemical detection of u-PAR, e.g. in immunostaining of cancer cells, such as in tissue sections at the invasive front, or 5) inhibits the binding of pro-u-PA and active u-PA and thereby inhibits cell surface plasminogen activation. Methods are disclosed 1) for detecting or quantifying u-PAR, 2) for targeting a diagnostic to a cell containing a u-PAR on the surface, 3) for preventing or counteracting proteolytic activity in a mammal. Methods for for selecting a substance suitable for inhibiting u-PA/u-PAR interaction, for preventing or counteracting localized proteolytical activity in a mammal, for inhibiting the invasion and/or metastasis comprise the use of the antibodies and of nude mice inoculated with human cancer cells which are known to invade and/or metastasize in mice and having a distinct color, f.x. obtained by means of an enzyme and a chromogenic substrate for the enzyme, the color being different from the cells of the mouse.

摘要翻译： 针对尿激酶纤溶酶原激活剂受体（u-PAR）的单克隆或多克隆抗体或其子序列，类似物或糖基化变体。 公开了与游离u-PAR或与u-PA和u-PAR之间的复合物反应的抗体，其能够1）在ELISA中捕获u-PAR，或2）检测u-PAR，例如， 或3）在放射免疫沉淀测定中，沉淀纯化的u-PAR以完整或片段形式存在，或4）可用于u-PAR的免疫组织化学检测。 在诸如在侵入性前沿的组织切片中的癌细胞的免疫染色中，或5）抑制pro-u-PA和活性u-PA的结合，从而抑制细胞表面纤溶酶原激活。 公开了用于检测或定量u-PAR的方法，2）用于将诊断靶向到表面上含有u-PAR的细胞，3）用于预防或抵消哺乳动物中的蛋白水解活性。 用于选择适于抑制u-PA / u-PAR相互作用的物质，用于预防或抵消哺乳动物中局部蛋白质分解活性，抑制侵袭和/或转移的物质的方法包括使用抗体和接种人的裸鼠 已知在小鼠中侵入和/或转移并具有不同颜色的癌细胞，fx 通过酶和酶的显色底物获得，颜色不同于小鼠的细胞。