ד"ר אלה פישמן - TARGETED Fc2’-3-PE40 CHIMERIC PROTEIN ABOLISHES PASSIVE CUTANEOUS ANAPHYLAXIS IN MICE

Cells like basophils and mast cells play a crucial role in allergic reactions when their high-affinity FceRI receptor interacts with mammalian antibody IgE. Targetting of cells expressing these receptors using a chimeric or fusion protein thus becomes an attractive approach in designing immunotherapeutics towards allergies. One such which was made by fusing mouse IgE Fc fragment and Pseudomonas exotoxin (PE) not only killed cultured mouse mast cells effectively by inhibiting protein synthesis, it also showed the same effect in vivo or within the living animal. This chimeric protein successfully prevented the development of skin allergy called as passive cutaneous anaphylaxis reaction (PCA) in mice, keeping the plasma histamine levels of the treated animals at control levels. A mutated, enzymatically inactive analogue of this chimeric protein Fc_2’-3-PE₄₀, Fc_2’-3-PE_40M on the other hand could not show such effect. However, Fc_2’-3-PE₄₀ was effective in blocking the allergic reaction to 80% even in a single dose. A pretreatment of mice with this protein before the exposure to allergens could achieve 100% prevention of the allergic response. The experiments showed that this blocking effect is induced within few hours. Hence the application of Fc_2’-3-PE₄₀ as a novel agent for the treatment of allergic disorders warrants attention as it is able to rapidly arrest the allergic reaction after the appearance of clinical symptoms and thus can be very helpful in treating the allergic emergencies. Some other researches have shown that the basophil and mast cells’ death induced by Fc_2’-3-PE₄₀ is ‘apoptotic’ in nature, thus preventing the leakage of their contents and avoiding degranulation of the cells. This chimeric protein can be developed as new generation treatment as it shows clinical superiority over other major groups of drugs like b2-agonists, methylxantines, glucocorticoids, antihistamines and chromolyn sodium etc. which are unable to prevent the allergic reaction and can only reverse or block its effects and also have side-effects. The use of similar chimeric molecules will offer a new hope for treatment of various other diseases like cancer.