"A room from hell" is how most of the 5 million to 10 millionAmericans who are allergic to cats would doubtless describe theisolation ward at a certain medical center. Its occupants are notpeople, but cats. Enough felines inhabit this room to ensure that itsfloor and furnishings are saturated with the antigen disseminated byFelis domesticus. Yet 72 such human sufferers are of their ownaccord doing time in just such a chamber.
An estimated 55 million "owned" cats dwell in some 30 millionAmerican households, according to Andrew Rowan, director of theCenter for Animals and Public Policy at Tufts University. An equalnumber of unowned felines live on their own.
Contrary to popular belief, Rowan told BioWorld, a cat's allergenicprotein is not its dander but its saliva. "When an animal licks its coatclean," Rowan explained, "it deposits the allergen on the dander." Theonly remedy he knows would be to bathe a cat every day, "which itprobably wouldn't appreciate."
A more molecular antidote to cat allergy is being tested now at twoundisclosed medical centers whose immunology departments areequipped with "cat rooms." The Phase II trial is enlisting 72susceptible patients in whom proximity to felines provokes nasalcongestion, asthmatic symptoms and bronchial spasm. "It's definitelya unique type of reaction you can get toward cats," observed RichardSmall, chief financial officer of ImmuLogic Pharmaceutical Corp.(NASDAQ:IMUL) of Cambridge, Mass.
Asked if ImmuLogic faces any competitors, Small replied, "Nobodyelse has taken this approach."
His company is sponsoring the human studies to gauge the ability ofits proprietary CatVax agent to induce tolerance to the offendingallergen in people as it has in mice. The 72 volunteers will actuallyenter the infernal, cat-contaminated chambers fortified by threeascending doses of CatVax or placebo. Small said the companyexpects to submit Phase II results to the FDA in the first quarter of1994.
Phase I experiments have already confirmed that the product is safe.
It worked in mice primed to serve as animal models for the humanallergic reaction to feline pets, as reported in the current Proceedingsof the National Academy of Science (PNAS). A team of immunologistsat ImmuLogic presented their animal results in an article titled"Peripheral T-cell tolerance induced in naive and primed mice bysubcutaneous injection of peptides from the major cat proteinallergen in humans, Fel d I."
As described, native Fel d I protein is the quintessential essence ofcat allergen. As starting material, the researchers took house dustfrom the vacuum-cleaner bags of homes with multiple cats in thefamily. Solubilized, lyophilized and extracted, the material next wentthrough a column of fixed monoclonal antibodies specific for Fel d I.
The team then cloned and expressed the molecule's two chains. Fromchain 1 they synthesized two 27-amino-acid peptides, whichbetween them elicit nearly all of the human T cell's immuneresponse to the cat allergen. These peptides are the active ingredientin the CatVax tolerizer.
When the immune system of an allergy sufferer faces a felineaffront, T cells take two countermeasures: one, they proliferate; two,they deploy cytokines -- mainly interleukins 2 and 4, plus gamma-interferon -- to beef up the B cells' antibody-generation. Unable totell friend from foe, these cytokines overreact and inflame the liningsof eyes, nose and airways.
Mice pretreated with the pair of peptides and then challengedsubcutaneously with the full chain 1 of the Fel d I molecule producedfewer T cells and cytokines than their peers injected with salineplacebo.
"I think there are two key results," said immunologist JuliaGreenstein, principal co-author of the PNAS paper. "One is that usinga peptide from an antigen, in this case an allergen, you can inducetolerance to a larger allergen," she told BioWorld. "The other thing isyou can do this in a primed animal, which mimics the allergic diseasestate in humans."
Will this work in humans as it did in mice? "Nobody knows,"Greenstein said, "because we're still in the middle of a Phase II trial."
She pointed out that traditional desensitization using graduateddoses of the whole allergen "are actually dangerous. When you get tothe higher doses, there are cases of anaphylaxis, an acute, potentiallyfatal reaction triggered by Immunoglubulin E." Greenstein continued,"So if you could substitute a peptide, which is far less reactive withIgE, you would get rid of that side effect."
If the technique works in humans, the company plans to extend itspeptide-tolerizing strategy to other allergies and to autoimmunediseases. "The ability to tolerize T cell responses with subcutaneousinjections suggests a practical approach to treating human diseaseswith peptides containing T-cell epitopes," the PNAS report concluded.
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.