FOR IMMEDIATE RELEASE
March 16, 2000

New Immunological Approach to Glioblastoma Multiforme

Norris Cotton Cancer Center is testing a new immunological approach to treating the most common form of brain cancer, glioblastoma multiforme (GBM). GBM is a highly malignant fast-growing cancer of the brain cells, for which there is no curative treatment available. Neuro-oncologists at Norris Cotton Cancer Center see 25 to 30 new patients with GBM every year.

The test was designed at Dartmouth-Hitchcock's Norris Cotton Cancer Center in Lebanon, New Hampshire, by Camilo Fadul, M.D., Marc Pipas, M.D., Paul Wallace, Ph.D., and their colleagues. After six years of laboratory work, this research team has begun a clinical trial that infuses activated, armed immune cells directly into GBM tumor sites.

GBM cancers behave differently from most other tumors: They do not metastasize (spread) throughout the body, and they kill by growing back in the same place in the brain. Theoretically, therefore, an effective therapy can be delivered directly to the site of the brain cancer, without the need to treat the entire body. This peculiarity of GBM led researchers to develop killer cells specifically directed against GBM. These cells are then introduced directly into the tumor site and prevent or decrease regrowth of the tumor. With standard treatment of radiation following surgery, average survival time for patients with glioblastoma multiforme is only 12 to 18 months, because of tumor regrowth. The goal of this intratumoral immunotherapy is to extend life by killing the tumor cells that remain behind after surgery.

The process begins with leucophoresis and elutriation to obtain highly purified populations of monocytes (certain immune cells) from the patient's blood. These cells are grown in the laboratory in a bath of interferon, vitamin D, and GM-CSF (granulocyte-macrophage colony-stimulating factor) to convert them into activated macrophages (cells that that can attack and phagocytose, or "eat" tissue). Then, the activated macrophages (MAK™) are incubated with a bispecific antibody (MDX-447) that (1) recognizes a substance expressed on the membrane of the tumor cell - epidermal growth factor receptor(EGFr), and (2) recognizes a receptor, CD64, on the macrophage cell membrane. This process targets the macrophages to aggress only against GBM tumor cells - a high percentage of which express EGFr - and leave normal brain tissue unharmed. The resulting product is a preparation of macrophages specifically armed to bind to the GBM tumor. These macrophages are infused directly into the brain cavity left after surgical removal of the GBM tumor. The hope is that the armed macrophages will "seek and destroy" remaining GBM cells in the margins of the surgical cavity, thus preventing regrowth of the tumor, and prolonging life.

The Phase I trial of this approach began in December 1999. The purpose of a Phase I study is to find the best way to give a new treatment and how much of it can be given safely. The research team aims to recruit 12 more patients into the clinical trial. Queries for further information should be directed to the Neuro-Oncology Group at Norris Cotton Cancer Center, (603) 650-6312.

Referenced Dartmouth Medical School Clinical Trial: A Phase I trial of intratumoral bi-specific antibody and activated monocytes in patients with recurrent or refractory glioblastoma multiforme.

Support for the development and implementation of this clinical trial is provided by Medarex, Inc.; IDM; the American Cancer Society; and Norris Cotton Cancer Center.