Anergen Inc. announced Thursday that it has filed aninvestigational new drug (IND) application for a therapeuticpeptide vaccine for rheumatoid arthritis and expects to beginPhase I testing in the spring.

The vaccine, Anervax, uses a specific peptide sequence of themajor histocompatibility complex (MHC) molecule as atherapeutic vaccine. MHC is a protein found on the cell surfaceof antigen-presenting cells. John Fara, president and chiefexecutive officer of the Redwood City, Calif., company explainedthat injection of the peptide vaccine "elicits an antibodyresponse by the patient to block presentation of the antigeninvolved in rheumatoid arthritis to the patient's T cells bysterichindrance." Antigens activate T cells that recognize theantigen, triggering a cascade of events that lead toinflammation and other manifestations of rheumatoid arthritis.

The antibodies elicited by the vaccine are specific to the MHCthat is presenting the antigens involved in rheumatoidarthritis; they act to block the interaction of MHC peptideantigen with the T cell receptor. Anergen hopes that byblocking presentation of the antigen it can halt progression ofthe disease.

While it is not known which antigens are involved inrheumatoid arthritis, Fara said this knowledge is not necessarysince the antibodies elicited by the vaccine are directed to theMHC rather than specific peptides.

The vaccine technology was developed initially in the lab ofVanderbilt University Medical Center professor SubramanianSriram. Anergen obtained an exclusive license from Sriram andfiled a patent application on the technology.

Anergen said the Anervax vaccine complements its coreAnergix technology, which links an antigenic epitope -- theportion of a disease-causing peptide that is recognized by the Tcell -- to a soluble form of MHC. This compound binds tospecific T cell receptors and induces anergy, or non-responsiveness, in the T cells bearing the receptor, thus turningoff the T cells.

Anergen (NASDAQ:ANRG) is developing Anergix therapies forautoimmune diseases, including multiple sclerosis, myastheniagravis and Type 1 diabetes. Last August the company enteredan agreement with Novo Nordisk A/S to develop products forthese three diseases. Novo has rights to worldwide sales offuture products and Anergen has rights to co-promote productsfor multiple sclerosis (MS) and myasthenia gravis (MG) in theU.S. Anergix therapies for MS and MG are now in pilot clinicals.

Fara said Anergen plans to retain exclusive U.S. rights toproducts covered in any future agreements. The companyintends to further develop the Anervax vaccine before seekingany licensing arrangements.

Of the other companies working on a rheumatoid arthritisvaccine, Immune Response Corp. is the furthest along; its T cellreceptor-based vaccine entered Phase I/II clinicals in 1992. Inaddition, MedClone Inc. is in development with a MAb HRF1vaccine therapy and T Cell Sciences Inc. is in the researchphase with TM31 MAB for rheumatoid arthritis.

-- Brenda Sandburg News Editor

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