About 80,000 cases of melanoma and renal cell carcinoma are diagnosed in the U.S. each year.

IL-2 use is limited, however, by potentially life threatening side effects, including hypotension, particularly at the high-dosage level indicated for these end-stage cancers.

A majority of patients undergoing high-dosage IL-2 treatment currently either require intensive care unit (ICU) intervention and/or are unable to complete the full course of treatment.

But now, advanced skin and end-stage kidney cancer patients may have a better chance of survival with drugs developed from a new synthetic enzyme that significantly improves the effectiveness of existing IL-2 cancer therapy.

This is the finding of research presented Monday at the American Association for Cancer Research 92nd Annual Meeting in New Orleans, La.

In animal studies conducted by researchers at the Huntsman Cancer Institute in Salt Lake City, UT, and MetaPhore Pharmaceuticals in St. Louis, MO, the synthetic enzyme M40403 showed an ability to reverse the extreme blood-pressure drop that is a common side effect of high-dosage IL-2 cancer therapy.

The research also showed that the compound enhances the anti-cancer properties of IL-2 therapy.

Reseachers administered the synthetic enzyme, which mimics the action of a natural enzyme, superoxide dismutase (SOD), as a co-therapy with IL-2 in several animal models of advanced cancer.

Previous studies have confirmed that the synthetic enzyme effectively reproduces the free-radical fighting properties of the natural SOD enzyme, which has been found to be deficient in cancer states.

When in excess, free radicals -- particularly superoxide anions -- have been shown to deactivate a class of molecules, called catecholamines, which aid the body's natural blood pressure regulatory system.

By reducing superoxide, the synthetic SOD enzyme restores the levels of catecholamines necessary to constrict blood vessels and reverse hypotension.

Moreover, superoxide also inhibits the activity of NK cells, hampering the anti-tumor effect of IL-2.

"By restoring the body's natural vascular regulatory system, the synthetic SOD enzyme addresses a major limiting side effect of current IL-2 therapies. It also appears to work synergistically with IL-2's anti-cancer properties," said Dr. Wolfram Samlowski of the Huntsman Cancer Institute at the University of Utah.

In two separate animal models, as a co-therapy with IL-2, the synthetic SOD enzyme prevented the onset of IL-2 induced hypotension and enhanced IL-2's ability to kill malignant cells.

In an animal model of pulmonary metastasis, both the synthetic SOD enzyme and IL-2 appeared to have significant anti-tumor action, in combination and individually.

In the aggressive Meth A fibrosarcoma tumor model, co-therapy with IL-2 and the synthetic SOD enzyme resulted in a 50 percent complete remission rate, which lasted more than 90 days following tumor implantation, while mice treated with IL-2 therapy alone lived an average of 21 days following implantation with no remissions.

"These studies demonstrate that the synthetic SOD enzyme may have tremendous potential as a co-therapy with IL-2 and related cytokine cancer therapies," said Daniela Salvemini, MetaPhore's Vice President and Director of Pharmacology and co-investigator in the study.

Other members of the research team include Ryan Petersen and John Robert McGregor of the Huntsman Cancer Institute.

[Contact: Emily Ross]

28-Mar-2001