ANTIBODIES: Anti-Angiogenic Therapy Reduces Tumors - Brief Article

Applied Genetics News, April, 2000

ImClone Systems, Inc.(180 Varick St., New York, NY 10014 ; Tel: 212/645-1405, Fax: 212/645-2054, Website: www.imclone.com) released preclinical data on its anti-VEGFr monoclonal antibody. The company's monoclonal antibody targets a receptor of the vascular endothelial growth factor (VEGF) referred to as FLK-1 in mice and KDR in humans. The FLK-1/KDR receptor plays an important role in the formation of new blood vessels associated with tumor growth. The findings were presented at the 91st Annual Meeting of the American Association for Cancer Research (AACR), and will be published in the April 15th Edition of the Journal of Clinical Investigation.

In the study, the murine antibody DC101 was used in combination with low-dose chemotherapy (vinblastine) in immunodeficient mice inoculated with human neuroblastoma cells. The findings revealed that regular administration of the two therapies in combination produced regression of tumors with no recurrence during 180 days of treatment. Groups of five mice were inoculated with human neuroblastoma cells and randomized into four study arms: a control group, a single-therapy vinblastine group, a single-therapy DC101 group, and a combination treatment (vinblastine and DC101) group. Long term tumor regression was not achieved in the control or single-therapy groups.

"This preclinical study shows that low-dose chemotherapy in combination with our monoclonal antibody has a highly significant effect on the blood vessels supplying neuroblastoma tumors in mice," says Daniel J. Hicklin, senior director of immunology at ImClone Systems.

The study's treatment regimen was in contrast to the traditional approach of using high-dose chemotherapy for short duration. Despite the chronic nature of the treatment, there was no overt toxicity observed in the mice, according to the lead investigator of the study Robert Kerbel of Sunnybrook and Women's College Health Science Center (Toronto, Canada).

ImClone is evaluating the therapeutic potential of its lead anti-angiogenic cancer therapy, IMC-1C11, which is a chimeric antibody equivalent of DC101. A phase I clinical trial has been initiated.