HAIFA, Israel - A new chemokine-encoding DNA vaccine showed promise in laboratory animals of halting the damage in autoimmune diseases, such as multiple sclerosis (MS) and rheumatoid arthritis, caused by pro-inflammatory cytokines and chemokines. Nathan Karin, a senior research immunologist in the Technion Faculty of Medicine in Haifa, led a team that is poised to test this DNA vaccine in clinical trials.

This same manipulation of gene therapy already is in clinical trials to elicit protective immunity against microbial- and viral- induced diseases such as HIV. Karin extrapolated the idea of using DNA vaccination to break the tolerance in autoimmune disease about 10 years ago, published in a 1992 issue of Nature, following with a succession of research papers from which the technology was developed and patents are pending. Local and European biopharmas have "expressed interest in the technology," and Karin is discussing possible development with local biotechnology venture groups.

"We considered that chronic autoimmune diseases could be placed under control by immunizing patients with neutralizing antibodies directed against one or more of the proinflammatory peptides, self-products that are critical for the development and progression of the autoimmune condition," Karin told BioWorld International.

Recently, related clinical trials of antibodies against inflammation-causing cytokines have demonstrated an ability to inhibit rheumatoid arthritis. But Karin acknowledged these neutralizing antibodies require frequent administration, and that the immune system eventually raises an immune response against them that can exacerbate the disease.

The animal results of the Israeli group showing the effectiveness of a TNF-alpha DNA vaccine against an MS model were published in the August issue of the Journal of Clinical Investigations, and have expanded this application to rheumatoid arthritis.

Karin's novel approach utilizes a technology of naked DNA vaccination. That is, he introduced bioengineered genes of the target cytokine and chemokine peptides that were seen as foreign antigens that raised native neutralizing antibodies.

Karin has been working on self-generated antibodies as "a new way to re-endow the immune system with the ability to self-regulate antibody production as needed with autoimmune disease progression."

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