Synthetic enzyme wards off side effects

Cancers of the skin and kidney that have spread throughout the body are typically resistant to drug treatment, so researchers have turned to a compound called IL-2 to boost the body’s immune response against these tumors. However, IL-2 can cause life-threatening low blood pressure.

To counter that side effect, researchers are looking toward M40403, a synthetic enzyme. This compound mimics the action of superoxide dismutase, which constricts blood vessels and raises blood pressure. Mice given high doses of IL-2 experience significant blood pressure drops–from an average of 100 millimeters of mercury to less than 40 mm Hg. Adding M40403 to IL-2 treatment kept blood pressure normal, which enabled researchers to double the dose of IL-2 in animal tests.

Besides reducing IL-2’s side effects, M40403 exhibited anticancer activity, reports Wolfram E. Samlowski of the Huntsman Cancer Institute at the University of Utah in Salt Lake City. “It was a nice bonus,” he says.

Compared with either drug alone, IL-2 and M40403 together were better at reducing the spread of cancer in mice. The combo also lengthened survival time of mice injected with cancer cells from an average of 20 days to more than 120 days. “These effects are practically unheard of,” says Samlowski, who intends next to study M40403 in people.

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