By David N. Leff

Five kinds of immunoglobulin — G, A, M, D and E — swarm in mammalian blood, poised to dispatch antibodies against alien antigens. The scarcest is immunoglobulin epsilon, a.k.a. IgE. It accounts for less than one one-hundredth of 1 percent of serum immunoglobulins. But IgE is big in clinical trials aimed at eliminating it from patients with asthma and hay fever.

Three companies are collaborating in these anti-IgE studies: Tanox Biosystems Inc., in Houston; Genentech Inc., of South San Francisco, and Novartis AG, of Basel, Switzerland. (See BioWorld Today, July 10, 1996, p. 2.)

"This three-way collaboration has several clinical trials in progress," said George Wang, Tanox's vice president of process development and production. "Results of Genentech's asthma study are due out next month," he told BioWorld Today. "Tanox and Novartis have two asthma trials in progress. One is a Phase IIA study of Tanox's chimeric antibody against mountain cedar pollen, of which results are coming in now."

This was the chimeric antibody that Tanox tested successfully on 150 Texas hayfever sufferers in 1995. (See BioWorld Today, Feb. 14 , 1996, p. 1.)

The second Tanox/Novartis trial, Wang continued, "involves switching from the chimeric antibody to a humanized antibody, and from intravenous infusions to a one-shot, high-strength subcutaneous injection. This was a Phase I study, already completed. We are now analyzing its results."

All of this therapeutic action is directed against the least immunoglobulin, the vanishingly small IgE, generally indicted as principal perpetrator of asthma and allergy.

But pediatric allergist Hans Oettgen, at Children's Hospital, in Boston, finds that knockout mice devoid of IgE are far from lacking in the two key pathogenic hallmarks of asthma. His paper in the current Proceedings of the National Academy of Sciences (PNAS), dated Feb. 18, 1997, bears the title: "Allergen-induced bronchial hyperreactivity and eosinophilic inflammation occur in the absence of IgE in a mouse model of asthma."

Oettgen sensitized his IgE-minus mice, and wild-type controls, with Aspergillus fumigatus, by spraying this notoriously allergenic fungus into their nostrils. Both groups developed severe bronchial smooth-muscle contraction and eosinophilia inflammation of the airways.

Still, Oettgen told BioWorld Today, "we're several steps away from making any conclusion about the correlation between IgE and asthma in humans. But these results certainly tell us that you can get bronchial hyper-responsiveness and eosinophilic inflammation without IgE."

He defined bronchial hyper-responsiveness as affecting "a person with asthma who breathes cold air and then wheezes. That's a non-specific irritant."

Oettgen now plans to employ his IgE-negative mouse model to look into another version of asthma, the acute bronchial response, "in which, for example, a person with asthma who is allergic to cats walks into Grandma's house where there's a cat, and then starts wheezing. That's an immune response.

The benefit of studies like these," Oettgen concluded, "is by ruling things in or out, critical or not critical. As more and more information accumulates with regards to the functions of individual molecules in cell types and asthma pathogenesis it may become possible to have intelligent drug design. But our study is a tiny little piece of a huge thing." *

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