991039 Canadian Scientists Using E.Coli to Kill CancerOctober 16, 1999Cambridge, MA - A toxin produced by the deadly E. coli bacteria most commonly linked to illness caused by undercooked meat has been used to rid bone marrow of cancer cells for the first time by a research team led by scientists at Princess Margaret Hospital's Ontario Cancer Institute, the Cross Cancer Institute and the University of Alberta. The dangerous toxin could be effective in completely purging all traces of cancer in a patient's stem cell graft, greatly improving the success of autologous stem cell transplants in patients with some cancers. The finding paves the way for future research into improved treatments for some particularly deadly forms of cancer such as non-Hodgkin's lymphoma, multiple myeloma, and breast cancer. A group in Toronto led by Princess Margaret Hospital's Dr. Jean Gariepy originally pioneered the new technique. It is expected to reduce the likelihood of re-infusing diseased cells back into patients suffering from breast cancer, lymphoma and multiple myeloma. Researchers have been grappling with a major problem -- mainly, that the failure of high-dose chemotherapy with stem cell transplantation may be caused, at least partly, by the re-infusion of contaminated tumor cells in the stem cell graft. The researchers are using a toxin called SLT-1 to clean blood cells of cancer cells by using a receptor on the surface of the cancer cells recognized by the toxin. The toxin is then removed from blood cells prior to re-infusing the stem cells back into cancer patients. The researchers found that while the toxin kills a broad range of cancer cells, particularly breast, lymphoma and multiple myeloma cells, it does not kill healthy blood stem cells. University of Alberta Oncology Professor Linda Pilarski and colleagues in Edmonton and Toronto have studied the use of this “purging agent” to kill the malignant cells in multiple myeloma patients and leaving the normal stem cells intact. “We've shown that myeloma cells are effectively purged by SLT-1 -- a ribosome inactivating toxin -- and that the normal stem cells survive. This means it is potentially safe to use as a purging agent for the graft before re- infusing it into the patient,” Dr. Pilarski says. “There is a lot more work to be done, to refine the technique and to ensure safety, but this could prove to be an important advance for myeloma patients and perhaps other patients treated with autologous transplants such as lymphoma and breast cancer patients.” Multiple myeloma, a cancer of the immune system located in the bone marrow, is incurable with an average survival of only three to four years. Even though patients usually respond to chemotherapy, they nearly always relapse. They are treated with high-dose chemotherapy to kill off malignant cells. Then they are transplanted with white blood cells, taken from the patient usually when the disease is in remission. Cancer researchers know, however, that some of the malignant cells are being transplanted back into patients. Moreover, graft cells have been shown to cause myeloma. Principal investigator Dr. Jean Gariepy, a professor in the Department of Biophysics, University of Toronto, and a Senior Scientist at Princess Margaret Hospital's Ontario Cancer Institute, says, “In particular, the use of the toxin as an agent to clean a patient's stem cells contaminated with cancerous cells, seems well suited to patients with multiple myeloma. Our group has seized an opportunity to use a deadly bacterial toxin responsible for hamburger disease to treat a variety of cancer patients.” Dr. Andrew Belch, a professor in the Department of Oncology, University of Alberta, points out that having a “clean” graft may improve survival. “In studies using identical twin grafts, patient survival appears to be better than that when the patient's own cells are used for the graft, probably because the graft from the healthy twin is disease-free. We hope that toxin-based purging will provide a disease-free graft for the majority of patients who have no twin.” Dr. Pilarski, Dr. Gariepy and Dr. Belch were recently awarded a Terry Fox New Frontiers Grant to improve the new technique and pioneer it in the clinic. Dr. Gariepy's work was supported by a translational research grant from the Leukemia Society of America. The work of Drs. Pilarski and Belch, both of whom work at the Cross Cancer Institute, was supported by the Medical Research Council of Canada and the Cancer Research Society. The results of the study will be published in the October 15 issue of the journal, Blood. The Princess Margaret Hospital, a teaching hospital of the University of Toronto, has achieved an international reputation as a global leader in the fight against cancer and is considered one of the top comprehensive cancer treatment and research centers in the world. Located in Toronto, Canada, Princes Margaret Hospital and its research institute the Ontario Cancer Institute is a member of the University Health Network, which also includes the Toronto General Hospital and the Toronto Western Hospital. On February 25, 1998, SELECT Therapeutics announced that it entered into a license and research agreement with the Ontario Cancer Institute (OCI, Toronto) and the University of Toronto Innovation Foundation to develop improved interventions for cancer patients whose therapies include autologous stem cell transplantations. The license grants SELECT exclusive worldwide rights to use the invention, and manufacture products based on the invention, in return for royalties and research support to the Ontario Cancer Institute. The invention is the subject of patent claims which have been allowed.
|
