Targeted Protein Toxin Effective Against Persistent Brain Tumors

November 24, 1997

Scientists at the National Institutes of Health have developed a new drug that can reduce the size of some persistent brain tumors without causing severe side effects. A report of the first clinical trial of this drug, called transferrin-CRM107, will appear in the December 1997 issue of Nature Medicine.

In the clinical trial(1), researchers led by Edward H. Oldfield, M.D., of the National Institute of Neurological Disorders and Stroke (NINDS), used a special pressurized pump to deliver transferrin-CRM107 directly to the tumor. This drug is a compound created by linking diphtheria toxin to a protein called transferrin that targets rapidly growing cells such as tumor cells. Nine of the 15 patients who were evaluated after this treatment had reductions in tumor size, and the tumor disappeared completely in two patients. While these results are promising, much more work remains before the drug may be ready for market approval.

In a related study in the same issue of Nature Medicine,(2) NINDS investigators led by Dr. Oldfield and colleagues from the National Cancer Institute and the National Human Genome Research Institute report on the first clinical trial of another new therapy, which uses virus-producing cells to deliver a herpes virus gene that increases tumor cells' sensitivity to the antiviral drug ganciclovir. The patients were later treated with ganciclovir to kill the tumor cells. However, this therapy worked only against very small tumors in four of the 15 patients who were evaluated.

The NINDS, one of the National Institutes of Health located in Bethesda, Maryland, supports a variety of research focused on improving the diagnosis and treatment of brain tumors. It is the nation's leading supporter of research on the brain and nervous system and a lead agency for the Congressionally designated Decade of the Brain.

(1) Laske, D.W.; Youle, R.J.; Oldfield, E.H. "Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors." Nature Medicine, Vol. 3, No. 12, December 1997, pp. 1362-1368.

(2) Ram, Z.; Culver, K.W.; Oshiro, E.M.; Viola, J.J.; DeVroom, H.L.; Otto, E.; Long, Z.; Chiang, Y.; McGarrity, G.J.; Muul, L.M.; Katz, D.; Blaese, R.M.; Oldfield, E.H. "Therapy of malignant brain tumors by intratumoral implantation of retroviral vector producing cells to transfer the herpes simplex-thymidine kinase gene and intravenous ganciclovir." Nature Medicine, Vol. 3, No. 12, December 1997, pp. 1354-1361.

NIH/National Institute of Neurological Disorders and Stroke

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