Protecting The Immune System From Itself

LIKE SOLDIERS IN WAR WHO turn on their commanders, the body's immune defenses can attack normal tissue, triggering diseases such as rheumatoid arthritis and multiple sclerosis. The problem is a communications breakdown between "helper" T cells and antibody-producing B cells, which normally cooperate to destroy invaders.

Two years ago, Dartmouth Medical School immunologist Randolph Noelle reported that he had halted such autoimmune reactions in mice with a monoclonal antibody--a protein that can bind to cells and block functions. Now, he has extended the technology to humans and licensed it to San Diego-based IDEC Pharmaceuticals Corp., a leader in making monoclonal antibodies for cancer and autoimmune disease.

The protein that Noelle isolated attaches to a site on T cells called gp39, which serves as a kind of communication link between T and B cells. In experiments with mice, Noelle found that the protein interrupts communications when it binds to the gp39 site. The mice then stop producing their own, marauding antibodies, and the disease symptoms vanish. Incredibly, when protein injections are terminated, the mice begin producing antibodies again--but the animals remain disease-free. In effect, Noelle says, the anti-gp39 protein "resets the mouse's immune system."

IDEC plans to "humanize" the anti-gp39 protein by splicing it with human DNA to produce a drug. Clinical trials could begin as early as 1997. The protein should block rogue antibodies in humans, says IDEC CEO William Rastetter. "And we'd also hope to see the suppression continue."

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