IL-13 Used to Deliver Bacterial Toxin to Brain Tumors in Mice

HERSHEY, Pennsylvania—An innovative approach to treating glioblastoma multiforme—the use of a bacterial toxin attached to interleukin-13 (IL-13)—has been tested in animals, and a phase I study should begin this year, Waldemar Debinski, MD, PhD, said at the annual seminar of the Council for the Advancement of Science Writing, a science journalists’ group.

Dr. Debinski, assistant professor of surgery and of microbiology and immunology at Pennsylvania State University, where the agent is being developed, emphasized that “there are no effective treatments available” for glioblastoma multiforme, a high-grade glioma. Mean survival has increased only from 6 to 9 months in 1932, to less than 12 months in 1989. “After 2 years from diagnosis, almost all patients have died,” he said.

The new approach to treating glioblastomas emerged from a discovery by Dr. Debinski’s team regarding IL-13, a growth-hormone-like cytokine (see figure). They found that among more than 60 individuals with high-grade gliomas, “the vast majority of patients overexpressed the receptor for inter-leukin-13.”

Previous to this finding, no tumor-specific antigens or receptors were known to be overexpressed in glioblastoma multiforme cells to such an extent.

This discovery led to the idea of incorporating a Pseudomonas toxin into IL-13 as a way of delivering a killer dose to the cancer cells. Studies showed that among mice implanted with human gliomas and then treated with the toxin-IL-13 combination, 40% remained alive at 5 months, while control mice survived only 6 weeks.

Dr. Debinski hopes that the phase I trial will begin at a number of institutions in the summer of 2000. “We have a collaborative agreement with the brain tumor consortium supported by the NCI,” he said.