ZymoGenetics, Inc. reported that a phase 1 clinical trial is underway using Interleukin 21 (IL-21) in combination with the monoclonal antibody Rituxan. The open label dose-escalation trial is enrolling patients with advanced non- Hodgkin's lymphoma in a multi-site study conducted in the US patients will be treated with Rituxan and IL-21 once weekly for four weeks. Responding patients will be offered the combination regimen for four additional weeks.

"Patients need better treatments to fight cancer," said Bruce L. A. Carter, Ph.D., president and chief executive officer of ZymoGenetics. "We believe IL-21 in combination with Rituxan could offer an improvement over current therapies because in preclinical studies, IL-21 enhanced natural killer cell activity and improved monoclonal antibody anti-tumour activity."

The primary objective of the study is to evaluate the safety and tolerability of IL-21 when administered with Rituxan. Secondary objectives are to characterize the pharmacokinetics, immunogenicity and preliminary evidence of tumour activity of this combination.

Preclinical research into this combination offers compelling evidence for entering clinical trials, largely because IL-21 appears to enhance a principal mechanism by which Rituxan is thought to work. At ASH 2005, ZymoGenetics presented the results of preclinical research on IL-21's ability to enhance Rituxan-mediated killing of B-lymphoma cell lines. In these studies, after 90 days of follow-up, a combination of IL-21 plus low-dose Rituxan enabled survival of 70 per cent of mice injected with an aggressive non-Hodgkin's lymphoma cell line, compared with only 10 per cent that were treated with the same dose of Rituxan alone, and none that were treated with IL-21 alone.

Interleukin 21 (IL-21) has potent biological activity in regulating key classes of immune cells, including cytotoxic T cells and NK cells. These cell types play key roles in surveillance of the body to eliminate malignant and infected cells. Based upon the ability of IL-21 to inhibit tumour growth in a number of animal models, ZymoGenetics is developing IL-21 for the treatment of cancer and has retained commercialization rights for IL-21 in North America. The company has licensed commercialization rights outside of North America to Novo Nordisk A/S.