Chimeric Immunotherapy Blocks Cat Allergy

Researchers have designed and tested a chimeric human-cat fusion protein that successfully prevented inflammatory reactions to cat allergens in both laboratory cell cultures and mouse models.

Investigators at the University of California, Los Angeles (USA) prepared a molecule that combined a fragment of human IgG (Fc-gamma1) and the major cat allergen Fel d1. They coined the name GFD for the new molecule.

Their paper in the April 2005 issue of Nature Medicine reported that when GFD was added to cultures of white blood cells from individuals who were allergic to cats, it induced dose-dependent inhibition of Fel d1-driven IgE-mediated histamine release. This inhibition was associated with altered Syk and ERK signaling.

"We measured more than 90% less histamine in the cultures with GFD,” explained senior author Dr. Andrew Saxon, professor of clinical immunology and allergy at the University of California, Los Angeles. "Those results suggested that GFD successfully prevented the immune cells from reacting to cat allergen. The next step was to test GFD in mice that we had made allergic to the allergenic protein found in cat saliva and dander.”

GFD blocked reactivity to cat allergens in transgenic mice passively sensitized with human IgE antibody to cat and in Balb/c mice actively sensitized against Fel d1. GFD by itself did not trigger an allergic response.

These results suggest that chimeric human Fc-gamma-allergen fusion proteins may provide a new therapeutic platform for the immune-based therapy of allergic disease.




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