AIDSWEEKLY Plus, 26 August 1996
Daniel J. DeNoon, Senior Editor

Researchers have found that KS cells express extremely high levels of the interleukin 13 (IL-13) receptor.

Taking advantage of this finding, they created an immunotoxin that combines IL-13 with the cytopathic moiety of Pseudomonas endotoxin. This toxin selectively kills KS cells in vitro.

"IL-13 receptors on AIDS-KS tumors represent a novel plasma membrane protein for targeting with a potent cytotoxic agent such as Pseudomonas toxin-based chimeric protein," said Syed R. Husain of the U.S. Food and Drug Administration (FDA) Center for Biologics Evaluation and Research, Bethesda, Maryland.

Husain presented the findings at the XI International Conference on AIDS, held July 7-12, 1996 in Vancouver, British Columbia, Canada.

Husain noted that IL-13 is a pleiotropic immunoregulatory cytokine produced primarily by activated lymphocytes.

"It has a variety of effects on many different cell types including monocytes, B lymphocytes, and mast cells," he said. "It also has been shown to suppress HIV replication in human monocyte-derived macrophages."

Because renal carcinoma cells express high levels of the IL-13 receptor, Husain and colleagues used binding assays to search for the receptor in KS cells cultured from AIDS patients.

They examined six different AIDS-KS cell lines. "All KS cells expressed high-levels of a single class of IL-13 receptors, ranging from 2,500 sites per cell to 15,000 per cell," Husain reported.

Normal human endothelial cells expressed very low levels of the receptor: no more than 200 sites per cell.

Although IL-4 had been thought to share an affinity for the IL-13 receptor, the researchers found that IL-4 did not compete with radiolabeled IL-13 for binding to the receptor.

"The IL-13 receptor may be independent of the IL-4 receptor expression," Husain suggested.

The chimeric immunotoxin created to bind to the IL-13 receptor - dubbed IL-13-PE38QQR - was made by linking IL-13 to a mutated form of Pseudomonas endotoxin.

IL-13-PE38QQR completely inhibited the in vitro growth of KS cells at a concentration of 200 ng/ml. Concentrations ranging from 2.5 to 263 ng/ml achieved 50 percent inhibition of protein synthesis in the six AIDS-KS cultures.

Excess IL-13 abolished the cytotoxic effect of IL-13-PE38QQR, but IL-4 did not block the lethal effects of the immunotoxin.

Even at a concentration of 1,000 ng/ml, the toxin did not kill human endothelial cells.

Husain and colleagues are currently testing the toxin in an animal model of KS.

They noted that the IL-13 receptor not only provides a point of attack on AIDS-KS, but also offers a means of diagnosing the tumor.

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