Volunteers with high levels of globulins associated with allergicreactions have started receiving a new monoclonal antibody(MAb) in a Phase I safety trial by Tanox Biosystems Inc. andCiba-Geigy Ltd.The trial will primarily evaluate how well the MAb is tolerated,but will also assess the compound's ability to lower serumlevels of immune globulin IgE and will explore the effect oflower IgE levels on the patients' reaction to skin allergens.

The privately held Houston biotechnology company and Ciba-Geigy merged their anti-IgE research in 1990. Ciba-Geigy ofBasel, Switzerland, took a minority interest in Tanox, agreeingto purchase shares of common stock under undisclosed termsover four years.The use of a MAb against an endogenous immunoglobulin isbased on the observation that IgE does not seem to be essentialfor health, explained David Anderson, Tanox's executive vicepresident. People with low or undetectable levels of IgE areknown to live normally. However, levels of IgE generally arehigher in allergic patients, and IgE levels can be correlated withdisease severity.

The MAbs under study are designed to eliminate circulatingIgE and IgE-producing B cells without reacting with IgE that ispresent on the surface of basophils and mast cells.

In such allergic reactions as hay fever, insect stings andasthma, allergens may cause a cross-linking of IgE molecules onthe surface of basophils and mast cells. This activates a cascadeof biochemical events, including the release of histamine,creating symptoms associated with these allergic reactions.

Intercepting IgE and IgE-producing B cells comes later in thecascade of allergic reaction than a MAb produced by AllergeneInc. of San Mateo, Calif. Allergene is a private company that istesting molecular "images" of allergens, anti-idiotypicantibodies, in mice to assess down-regulation of the animals'immune reaction.However, Genentech Inc. has a preclinical program with ahumanized IgE MAb intended to treat allergic rhinitis orasthma, spokesman Geoff Teeter said.

"They're basically, as best I can figure, following in our tracks,"Anderson said about the IgE work at Genentech.

Preclinical work by Tanox and Ciba-Geigy indicates that theMAb removes circulating IgE and mediates certain immunereactions that should eliminate or suppress the B cellsresponsible for producing IgE.

The compound is referred to as CGP 51901 by Ciba-Geigy andas AL-901 by Tanox. The double-blind clinical trial inSouthampton, England, is taking place under permission fromthe United Kingdom; FDA has approved the investigational newdrug application.

Thirty-six volunteers with elevated IgE levels will be dividedinto four groups of nine people each, with six receiving thecompound and three receiving placebo in each group.

-- Nancy Garcia Associate Editor

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