Immune Mighty Mouse

Researchers have created a breed of mouse whose immune system can, in theory, churn out human antibodies against nearly any foreign protein. Called Xenomouse and described in this month's issue of Nature Genetics, the mouse could become a miniature factory easily retooled to produce antibody arsenals that target different microbial invaders.

Aya Jakobovits and her colleagues at Abgenix Inc., a biotech firm in Foster City, California, engineered the Xenomouse by replacing the mouse genes that code for different sets of antibodies with a stretch of human DNA that includes 139 genes, each of which codes for a different antibody component. The researchers tested these mice by injecting them with three foreign proteins: interleukin-8, epidermal growth factor receptor, and tumor necrosis factor-alpha. For each protein, the mice produced antibodies that bound to their targets almost as tightly as do antibodies produced in humans. "When we used to describe this project to people, it was like science fiction," says Jakobovits. "We never knew whether the antibodies would be functional."

Antibodies produced in the Xenomouse could be harvested from the spleen and injected into people suffering from infectious diseases or conditions with an autoimmune component, such as diabetes, in which the antibodies could target human proteins gone awry. A patient's immune system should be able to recognize the Xenomouse antibodies as human and refrain from attacking them, thus avoiding a problem that often crops up in people infused with antibodies made in conventional mice.

"It's going to revolutionize antibody treatments," says Richard Junghans, a molecular immunologist at Harvard Medical School in Boston. "No one's going to use mouse antibodies anymore." But with only three proteins tested, for now the mouse's might is mostly theoretical. Says immunologist Raju Kucherlapati of Albert Einstein College of Medicine in New York City, "It's important for a lot of people to get this mouse and make antibodies to really find out how well it works."

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