ATLANTA - Swedish researchers this summer will conduct theirfirst human trials with a treatment that couples an antigen with thecholera toxin B subunit, a powerful immunogen, to determine if theoral therapy has promise as a means for fighting autoimmunediseases, such as multiple sclerosis and rheumatoid arthritis.Cecil Czerkinsky, an immunologist with the University of Goteborgand the Karolinska Institute in Stockholm, told BioWorld Today thestudies in June will use an oral dose of the binding, non-toxic, Bsubunit of cholera toxin with tuberculin to see if the conjugate cangenerate an immune response.Researchers have recognized for years that oral administration ofantigens is an effective method of stimulating immunologicaltolerance, Czerkinsky said. However, it has been consideredimpractical because of the huge quantities of tolerogens needed tocreate even slight responses for short periods.He said he and his researchers decided to study the cholera toxinbecause it is one of the most powerful immunogens when deliveredorally."We cloned the cholera toxin and identified two main components,one responsible for binding and the other for toxicity," he said. "Thenwe just removed the toxic part and kept the binding activity."The idea, Czerkinsky added, is to use the non-toxic bindingcomponent - the B subunit of the cholera toxin - with antigensimplicated in autoimmune diseases to stimulate tolerance againstinflammatory T cell reactions.Czerkinsky presented results of preclinical studies with the cholera Bsubunit conjugate at the Experimental Biology `95 conference herelast week.He said animal studies aimed at testing the strategy against multiplesclerosis, rheumatoid arthritis and allograft transplant rejectionsshowed a single dose of the cholera B subunit coupled with antigenssuccessfully generated the immunological tolerances sought.In the multiple sclerosis studies, Czerkinsky said the cholera Bsubunit was conjugated with myelin basic protein (MBP) and whengiven orally cured MBP-induced experimental autoimmuneencephalomyelitis in rat models.Multiple sclerosis is a central nervous system disease resulting indamage to the myelin sheath, which is a protective coating aroundnerve fibers.Czerkinsky and his fellow researchers first presented their oraltolerance strategy last November in the Proceedings of the NationalAcademy of Sciences with an article titled, "Cholera toxin B subunit:An efficient transmucosal carrier-delivery system for induction ofperipheral immunological tolerance."They concluded "that a single oral administration of a small dose of asoluble or particulate antigen conjugated to the B subunit of choleratoxin, rather than abrogating systemic tolerance to conjugatedantigens, as generally assumed, can profoundly enhance it in naive aswell as in immune animals." n

-- Charles Craig

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