With microorganisms against brain tumors
Two new therapies against brain cancer have achieved good results in initial clinical tests with terminally ill patients. One method is based on pressure infusion of bacteriological toxins, the other uses modified herpes viruses to attack tumors. Both treatments have been shown to shrink brain tumors without serious side effects (December issue of Nature Medicine). Malignant gliomas are difficult to treat: They are located deep in the brain, where they are protected by the blood-brain barrier. To better attack them, Edward Oldfield and his colleagues at the National Institute of Neurological Disorders and Stroke developed a special pressure pump. It can deliver drugs through two small catheters that are inserted into the brain on opposite sides of the tumor.
In the experiment, the drug Tf-CRM107 was administered using the specially designed pump. Tf-CRM107 is a hybrid between the human protein transferrin, which transports iron to dividing cells, and a toxin from the diphtheria bacterium. Tumor cells have more iron receptors than normal cells. Therefore, the supplied transferrin primarily binds to cancer cells. Once the diphtheria poison it contains has entered the tumor cell, it infects it and makes it vulnerable to the immune system. 15 patients with recurrent and malignant gliomas who had not responded to conventional treatment methods such as radiation, chemotherapy or surgery were treated with such pressure infusions. After two weeks of infusions, the tumors in nine patients halved very quickly and then maintained that size for over 9 months. In two patients, the tumors disappeared completely, but only temporarily.
The second technique was also developed by Oldfield's group. It causes the tumor cells to increase their own sensitivity to drug therapies. To do this, the researchers injected mouse cells, which served as carriers of a genetically modified herpes simplex virus, into the brains of a second group of 15 patients with advanced gliomas. The herpes virus contains a gene that makes dividing tumor cells more sensitive to the drug ganciclovir. In four patients, tumors shrank by half, a reduction that lasted up to 11 weeks.
According to Robert Martuza, a neurologist at Georgetown University Medical Center, "These reports are the basis for further improvements." But he also pointed out that the methods still pose some problems. For example, the mouse cells equipped with the herpes virus cannot multiply and are therefore only effective for small tumors. And Tf-CRM107 also kills normal brain cells in high doses.
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