NCI’s TIL/TUMOR NECROSIS FACTOR GENE THERAPY STUDY has

Executive Summary

NCI's TIL/TUMOR NECROSIS FACTOR GENE THERAPY STUDY has enrolled three patients with advanced melanoma out of the up to 50 patients planned for inclusion in the trial. FDA approved a study protocol Nov. 13 to treat patients with an advanced stage of the skin cancer (prognosis of less than three months to live) with tumor-infiltrating lymphocytes (TILs) that have been altered to include the tumor necrosis factor (TNF)-producing gene. The study protocol got the go-ahead from the National Institutes of Health's Recombinant DNA Advisory Committee on July 31 but was on hold pending FDA approval for the first use of human gene therapy to treat cancer. The TNF gene is encoded into a virus which is used to enter the TIL cells. Those cells are then re-injected into the patient. Previous attempts to use the TNF protein as a systemic cancer treatment have resulted in serious toxicity problems. In the current study, the use of transduced TNF us intended to eliminate some of the toxicities because the TILs migrate to the site of a tumor. Patients in the study will be infused with the TNF-containing TIL in combination with interleukin-2 at once-a-week over a three week period. In later stages, the study will look at dose-escalating schedules, efficacy and side effects. The TNF for the National Cancer Institute study is being provided by Cetus, which designed the TNF virus and which also has an IL-2 product called Proleukin (see related T&G). The study will be led by NCI Surgery Branch Chief Steven Rosenberg, MD/PhD, as well as NCI's Michael Blaese, MD, and W. French Anderson, MD, of the National Heart, Lung and Blood Institute. Rosenberg has been studying unaltered TIL as a cancer therapy since 1987. The three researchers and NCI's Kenneth Culver, MD, have been involved since Sept. 14 in the first human gene therapy protocol, on adenosine deaminase (ADA) deficiency disease.