Show Me the Tumor

Like a mark of death, engineered proteins called monoclonal antibodies are supposed to stick to cancer cells and flag down immune fighters to destroy a tumor. But such a strategy, for some unknown reason, has generally failed. Now, scientists may have found a way to turn monoclonal antibodies into killing machines after all: by linking them together. The findings, reported in the current issue of the Proceedings of the National Academy of Sciences, suggest that antibody dimers could be a promising new approach to developing cancer treatments.

Those rare monoclonal antibodies that are able to kill cultured tumor cells appear to do so through an unexpected mechanism: Instead of attracting other immune cells, the antibodies trigger the tumor cell to stop dividing or to undergo apoptosis, or programmed cell death. A team led by Ellen Vitetta of the University of Texas Southwestern Medical Center in Dallas set out to examine this phenomenon in cells from Burkitt's lymphoma, a disease in which a kind of white blood cell called B lymphocytes divides uncontrollably, resulting in tumors throughout the body. Monoclonal antibodies designed to latch onto several different receptors on the lymphoma cells were almost powerless. In large quantities, however, an antibody to one receptor, CD19, showed a faint capacity for inhibiting cell growth. Some of these antibodies, the researchers found, had formed pairs; when separated out and tested alone, these dimers packed a powerful punch.

The researchers next tested dimers of monoclonal antibodies to other lymphoma receptors. All were better at arresting tumor cell growth or promoting cell death. The researchers also tried the anti-CD19 antibody in mice with human Burkitt's lymphoma tumors. Mice given the dimers, they found, lived up to 80% longer than mice given the monomers. "It's an interesting observation," says immunologist Martin Glennie of the University of Southampton, U.K., "but the mechanism remains obscure." Vitetta's team will try to figure that out in further tests in mice.

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