New Protein Proves Effective Against Kaposi's Sarcoma

February 26, 1997

Hershey, Pa. -- Laboratory tests recently revealed that a new, genetically engineered toxic protein is effective against Kaposi's sarcoma, the most common malignant complication of the AIDS virus, according to an advances in brief report in February's Clinical Cancer Research.

"It's amazing, but it's true," said Waldemar Debinski, M.D., Ph.D., director of tumor research in the Department of Surgery in the Division of Neurosurgery at Penn State's Milton S. Hershey Medical Center.

Lab tests showed that all five out of five Kaposi's sarcoma cell lines were highly and specifically sensitive to the toxic protein. In-vitro tests indicated very low concentrations of the toxic protein were required to kill the cancer cells. In-vivo tests on mice also showed pronounced anti-tumor activity.

Debinski generated the new protein in his lab, and in 1995 found it to be effective against brain cancer, one of the deadliest forms of cancer. The Food and Drug Administration, The National Cancer Institute, and Penn State are in the process of patenting the new compound, called IL 13-PE38QQR.

The substance is a combination of two proteins: interleukin 13, a naturally-occuring human protein which promotes the growth of white blood cells, and a genetically engineered bacterial toxin, Pseudomonas exotoxin A.

Certain cancer cells -- like brain cancer, Kaposi's sarcoma, and renal cancers -- have thousands of receptor sites that act as open doors to interleukin 13. The compound gains access to the cancer cell through the "doorway" of interleukin 13 and then attacks the cancer with the toxin.

The finding builds upon scientific developments from the past 15 years of research, a time during which the field of targeted therapy has evolved rapidly. An important discovery at the National Institutes of Health came when Debinski, working together with Ira Pastan and Raj K. Puri -- both of whom are coauthors on the current paper, found that almost all malignant cells "overexpress" receptors for interleukin 4. In other words, they have many receptor sites for the protein, making them very receptive to binding and penetration by that protein. Interleukin 4 is not identical to interleukin 13, but is very similar to it.

In addition to Hershey, several labs were involved in the current discovery of the new compound's effectiveness against Kaposi's sarcoma: The Food and Drug Administration's Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research; University of Southern California's School of Medicine; and the Laboratory of Molecular Biology, Division of Basic Sciences at the National Cancer Institute of the National Institutes of Health.###

Penn State

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