FCepsilon-PE, A CHEMICAL PROTEIN FOR THE OBJECTIVE TREATMENT OF ALLERGIC REACTIONS, A METHOD FOR THEIR MANUFACTURING AND PHARMACEUTICAL SUBSTANCES CONTAINING THE PROTEIN

摘要

The present invention generally relates to a new approach for the therapy of allergic responses, based on targeted elimination of cells expressing the FcepsilonRI receptor by a chimeric cytotoxin FcSUB2'-3/SUB-PESUB40/SUB. A sequence encoding amino acids 301-437 of the Fc region of the mouse IgE molecule was genetically fused to PESUB40/SUB-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 FcepsilonRI receptor, as well as primary mast cells derived from bone marrow. The present invention provides a chimeric protein for targeted elimination of FcSUBepsilon/SUBRI expressing cells especially useful for the therapy of allergic responses. The said chimeric protein is comprised of a cell targeting moiety for FcSUBepsilon/SUBRI 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 PESUB40/SUB, 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.