公开(公告)号：US20040043029A1

公开(公告)日：2004-03-04

申请号：US10336672

申请日：2003-01-02

申请人： Bristol-Myers Squibb Company

发明人： Ingegerg Hellstrom ,  Karl Erik Hellstrom ,  Kim Folger Bruce ,  George J. Schreiber

IPC分类号： A61K039/395 ,  C12N005/06 ,  C07K016/30

CPC分类号： G01N33/57484 ,  A61K38/00 ,  A61K47/6809 ,  A61K47/6811 ,  A61K47/6829 ,  A61K47/6851 ,  A61K49/0058 ,  A61K51/1045 ,  A61K51/1087 ,  A61K2123/00 ,  C07K14/415 ,  C07K16/30 ,  C07K2317/24 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/622 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/77 ,  C07K2319/00 ,  C12N15/10

摘要： The present invention relates to novel antibodies, antibody fragments and antibody conjugates and single-chain immunotoxins reactive with human carcinoma cells. More particularly, the antibodies, conjugates and single-chain immunotoxins of the invention include: a murine monoclonal antibody, BR96; a human/murine chimeric antibody, ChiBR96; a F(abnull)2 fragment of BR96; ChiBR96-PE, ChiBR96-LysPE40, ChiBR96 F(abnull)2-LysPE40 and ChiBR96 Fabnull-LysPE40 conjugates and recombinant BR96 sFv-PE40 immunotoxin. These molecules are reactive with a cell membrane antigen on the surface of human carcinomas. The BR96 antibody and its functional equivalents, displays a high degree of selectivity for carcinoma cells and possess the ability to mediate antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activity. In addition, the antibodies of the invention internalize within the carcinoma cells to which they bind and are therefore particularly useful for therapeutic applications, for example, as the antibody component of antibody-drug or antibody-toxin conjugates. The antibodies also have a unique feature in that they are cytotoxic when used in the unmodified form, at specified concentrations.

摘要翻译： 本发明涉及与人癌细胞反应的新型抗体，抗体片段和抗体缀合物和单链免疫毒素。 更具体地，本发明的抗体，缀合物和单链免疫毒素包括：鼠单克隆抗体BR96; 人/鼠嵌合抗体，ChiBR96; BR96的F（ab'）2片段; ChiBR96-PE，ChiBR96-LysPE40，ChiBR96F（ab'）2-LysPE40和ChiBR96 Fab'-LysPE40缀合物和重组BR96sFv-PE40免疫毒素。 这些分子与人类癌症表面的细胞膜抗原反应。 BR96抗体及其功能等同物对癌细胞显示出高度的选择性，并具有介导抗体依赖性细胞毒性和补体依赖性细胞毒活性的能力。 此外，本发明的抗体内在于它们结合的癌细胞内，因此特别可用于治疗应用，例如作为抗体药物或抗体 - 毒素缀合物的抗体组分。 抗体还具有独特的特征，因为当以指定浓度以未修饰的形式使用时，它们是细胞毒性的。