After 20 years of painstaking work, researchers have found a way to a kind of magic bullet to seek out and destroy cancer cells and cells infected with viruses such as HIV. The ammunition--immune system proteins known as antibodies--can be made in a test tube by a new cell line derived from normal and cancerous human white blood cells.
To ward off viruses, cancer cells, and other menaces, the immune system drafts a few brigades from a huge standing army of antibody-producing cells called B cells. Each brigade pumps out a unique antibody that recognizes and binds to a particular spot on the invader. Normally, blood from an infected person or animal will be loaded with various antibodies. But in 1975, researchers made mouse cell lines called hybridomas that generate a single type of antibody--a useful tool for identifying cellular proteins. These so-called monoclonal antibodies also helped physicians devise new diagnostic tests. But the mouse antibodies wouldn't seek and destroy invaders in humans, because the immune system often rejected them as foreign.
Intrigued, immunologist Abraham Karpas of Cambridge University and his colleagues worked for more than 20 years to find a way to make human cells specialize in monoclonal antibodies. Even making a mouse hybridoma is tricky: B cells from the spleen of an immunized mouse, which normally died out in culture dishes, must be fused with cancerous white blood cells called myelomas. But the human myeloma cells "wouldn't behave," Karpas says. The team spent years coaxing the cells to grow quickly in culture dishes and teasing out cells that could survive under the right conditions.
The resulting myeloma line enabled them to make nine different human hybridomas, each specializing in a particular antibody, including one that latches onto a key protein from HIV, the researchers report in the 13 February Proceedings of the National Academy of Sciences. The technique could now help researchers use B cells from tumor tissue to make anticancer antibodies, and B cells from HIV survivors to make antibodies that seek out and destroy the virus, Karpas says.
"It's an important development," says immunologist Gregory Adams of the Fox Chase Cancer Center in Philadelphia. The new cells will make it easier and cheaper to develop human antibodies, particularly for therapy, says immunologist Paul Nelson of the University of Wolverhampton, United Kingdom. "I think it's quite exciting," he says.