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Biotech / Medical : EntreMed (ENMD) -- Ignore unavailable to you. Want to Upgrade?

To: George Holt who wrote (1021)	5/17/1998 3:54:00 PM
From: George Holt	Read Replies (2) \| Respond to of 2135

New class of cancer drugs may help leukemia, too By Maggie Fox, Health and Science Correspondent WASHINGTON (Reuters) - A new class of cancer drugs that have recently won a great deal of attention because of their impact on tumors in mice may also work against leukemia, their discoverer says. Dr. Judah Folkman of Harvard University and Boston Children's Hospital, whose anti-angiogenesis compounds have made front-page news and tongue-twisting drug names a household word, said in a telephone interview Sunday he was surprised to find they worked against leukemia in mice. One of the drugs, endostatin, seems to put leukemia in remission when used alone in mice. And Folkman said he had found a third natural protein, called vasculostatin, to add to the growing arsenal of angiogenesis inhibitors. The angiogenesis inhibitors stop the formation of blood vessels that feed a tumor. The compounds, and there are more than a dozen in development, literally starve out a tumor. The hope is that they will be less toxic than current cancer therapy, which involves surgery and either strong chemicals or radiation that kill both the cancer cells and many healthy cells. But leukemia is a blood cancer that starts in the bone marrow and no tumors are involved. So how do the angiogenesis inhibitors work? ''The leukemia cells are like grapes growing on a bush and the branches are the blood vessels,'' Folkman told Reuters. ''The blood vessels we are talking about are thinner than a hair. They are called capillaries. The leukemia cells grow along those just like grapes do. What was found is that the leukemic cells stimulate new blood vessels in the bone marrow cavity and then grow on them,'' Folkman said. Folkman, Stephen Sallan of the Dana Farber Cancer Center, and Antonio Perez-Atayde published these findings more than a year ago in the American Journal of Pathology. Mice injected with mouse leukemia survived 40 percent longer when they also got TNP-470, one of the first angiogenesis inhibitors which is now being developed and tested by the National Cancer Institute (NCI) and TAP Pharmaceuticals Inc., a joint venture between Japan's Takeda Pharmaceuticals and Abbott Laboratories. What is new is that researchers working in Folkman's laboratory, led by Timothy Browder, have found that endostatin, one of the headline-winning compounds, has put the leukemia into remission in the mice. ''They remained without symptoms,'' Folkman said. ''We don't know if they are cured. We don't use the word cure.'' ''We're past 17 human years or something,'' Browder's work is unpublished, meaning it has not been submitted to one of the science or medical journals that usually vet such work. But it has been presented at a lecture at the National Cancer Institute. Some desperate leukemia patients could try TNP-470, Folkman said. ''The FDA (Food and Drug Administration) about a year ago approved a phase I trial to test TNP-470,'' Folkman said. Phase I trials test for safety in just a few patients, while Phase II trials, in a few more patients, test to see whether the new drug actually works. The trials are only open to children who have failed both drugs and bone marrow transplants. ''I don't think any have been entered because the failure rate (of bone marrow transplants) is so low,'' Folkman said. TNP-470 is also now in Phase I trials in patients with Kaposi's sarcoma, a kind of cancer marked by red skin blotches seen commonly in patients with AIDS and in Phase II trials in patients with some other tumors. The two compounds that have won recent attention, angiostatin and endostatin, are naturally produced by the body. When the drugs, which have been licensed to EntreMed Incare used together in mice that have been injected with tumors, the tumors appear to disappear. Reports about this have excited cancer patients, but Folkman points out that mice have different reactions to humans. The mice were injected with tumors rather than developing them naturally, which could affect results, and the proteins are very hard to produce and are unstable. They are a long way away from human tests and as yet the NCI is still trying to produce enough angiostatin and endostatin for testing in humans. They hope to get enough to test in about 30 patients, if approved, by the end of this year or early next year. Folkman said a researcher in his lab, Yuen Shing, has discovered a third natural angiogenesis inhibitor, known as vasculostatin. It is not even being tested in mice yet, but does show action against blood vessel cells in the laboratory. ''It just works in dishes,'' Folkman said. His lab is now searching for the gene that controls production of this protein. More information on Folkman's work is available on the Internet at www.childrenshospital.org. The NCI also has information on these and other cancer drugs on its page at www.cancertrials.nci.nih.gov. ^REUTERS@