Targeted Fc_2′-3-PE₄₀ chimeric protein abolishes passive cutaneous anaphylaxis in mice

The alarming increase in the incidence of allergic diseases in the past decade has led to a clear call for more effective treatment. Recently, we reported on the construction of a chimeric protein for targeted elimination of cells expressing FcεRI receptors. This chimeric protein, designated Fc_2′-3-PE₄₀, is composed of a Fc fragment of mouse IgE attached to a truncated form of Pseudomonas exotoxin. The Fc_2′-3-PE₄₀ chimeric protein was found to be highly cytotoxic to mouse mast cell lines and primary mouse mast cells. We now demonstrate that Fc_2′-3-PE₄₀ successfully prevents the development of passive cutaneous anaphylaxis reaction (PCA) in mice. Treatment with Fc_2′-3-PE₄₀ for 7 days prevented the PCA reaction in mice by 80% compared with that in control mice given only PBS. Fc_2′-3-PE_40M, the mutated, enzymatically inactive analogue of Fc_2′-3-PE₄₀, did not display this activity_. Fc_2′-3-PE₄₀ was also effective when given as a single dose 16 h before antigen exposure, resulting in complete inhibition of the PCA reaction. Moreover, treatment with Fc_2′-3-PE₄₀ did not cause mast cell degranulation, as the serum histamine values of mice treated with Fc_2′-3-PE₄₀ were within the range obtained for control, untreated mice. Thus, the Fc_2′-3-PE₄₀ chimeric protein offers a novel approach to the treatment of allergic disorders.