Protein nips mouse tumors in the bud.

Interleukin-12, the immune system messenger already showing great promise as a treatment for cancer, now appears to pack a double punch against tumors.

Judah Folkman, Emile E. Voest, and their colleagues at Children's Hospital in Boston, who already knew that IL-12 combats cancer by switching on the immune system's T cells, have found in tests with mice that "[IL-12] has another function. It inhibits or turns off new blood vessel growth," says Folkman. If tumors cannot grow new blood vessels, they can only reach a few millimeters in diameter.

Made by certain immune system cells, IL-12, a protein, normally circulates in the blood in low concentrations. Recently, it has sparked excitement among researchers by its ability to fight AIDS and parasitic infections, as well as cancer (SN: 8/20/94, p.120). Researchers have begun testing IL-12 as a cancer drug in humans.

But researchers have been puzzled by one finding, Folkman says. While IL-12 inhibits more than 20 kinds of tumors in mice, it doesn't kill tumor cells in laboratory dishes. This led his group to suspect that IL-12 curbs tumors indirectly, by slowing blood vessel growth, known as angiogenesis. They tested their idea by implanting a pellet containing a molecular growth factor in the corneas of mice.

This growth factor normally causes new blood vessels to creep across the cornea within days. Folkman's team found, however, that injections of IL-12 stopped new vessel growth almost completely -- even in two mouse strains that have deficient immune systems and therefore lack T cells. "This is a very potent angiogenesis inhibitor," Folkman says.

His team then gave IL-12 to mice bred to develop lung tumors and found that "the tumors stopped at less than BB size." The group reports its results in the April 19 Journal of the National Cancer Institute.

Other tests showed that IL-12 doesn't shut off vessel growth directly. Rather, it switches on another immune system protein, interferon gamma, that may in turn activate a protein that stops endothelial cells from growing. Giving mice interferon gamma rather than IL-12 proved less effective, apparently because IL-12 triggers a continuous supply of the interferon.

Finally, IL-12 worked even better combined with a second antiangiogenic drug, suggesting that more than one inhibitor should be used in cancer therapy.

In an accompanying comment, Robert S. Kerbel of the Toronto-Sunnybrook Regional Cancer Centre notes that researchers are finding evidence that many conventional antitumor drugs may work in part by inhibiting angiogenesis. These results give "a whole new meaning to the term 'magic bullet' in cancer," Kerbel writes, because they could lead to a new way to target tumors while sparing normal cells. "It's becoming an extremely hot topic," he says.