公开(公告)号：EP0868198B1

公开(公告)日：2004-03-10

申请号：EP96940708.9

申请日：1996-12-18

申请人： YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM

发明人： FISHMAN, Ala Medical School of Hadasa ,  YARKONI, Shai Medical School of Hadasa ,  LORBERBOUM-GALSKI, Haya Medical School of Hadasa

IPC分类号： A61K47/48

CPC分类号： C07K19/00 ,  A61K38/00 ,  A61K47/68 ,  A61K47/6829 ,  C07K2319/00

摘要： The present invention generally relates to a new approach for thetherapy of allergic responses, based on targeted elimination of cells expressing the Fc epsilon RI receptor by a chimeric cytotoxin Fc2'-3-PE40. A sequence encoding amino acids 301-437 of the Fc region of the mouse IgE molecule was genetically fused to PE40 - a truncated form of PE lacking the cell binding domain. The chimeric protein, produced in E. coli, specifically and efficiently kills mouse mast cell lines expressing the Fc epsilon RI receptor, as well as primary mast cells derived from bone marrow. The present invention provides a chimeric protein for targeted elimination of Fc epsilon RI expressing cells especially useful for the therapy of allergic responses. The said chimeric protein is comprised of a cell targeting moiety for Fc epsilon RI expressing cells and a cell killing moiety. The preferred killing moiety is the bacterial toxin Pseudomonas exotoxin (PE). This Pseudomonas exotoxin is a product of Pseudomonas aeruginosa. The present invention also relates to a method for the preparation of said protein. This chimeric protein is prepared by genetically fusing the Fc region of the mouse IgE molecule to PE40, a truncated form of PE lacking the cell binding domain. The present invention also provides pharmaceutical compositions, for the treatment of allergic diseases and for the treatment of hyperplasias and malignancies, comprising as an active ingredient the above mentioned chimeric protein and a conventional adjuvant product.