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)-PE₄₀(M), 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.