New data from a Phase I clinical trial led by Clark Chen, M.D., Ph.D., Lyle French Chair in Neurosurgery and Head of the University of Minnesota Medical School Department of Neurosurgery shows more than a quarter of patients with recurrent high-grade glioma, a form of brain cancer, were alive more than three years after treatment. "Given the deadly nature of this disease, three-year survival is rarely reported in the recurrent setting. It is notable that the survival benefit was seen across a range of patients and not just limited to patients with specific genetic mutations," said Dr. Chen. "This finding indicates that many patients could benefit from this treatment." As Dr. Chen explained in an October 27, 2017 presentation (http://www.abstractsonline.com/pp8/#!/4557/presentation/619) at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Philadelphia, two steps were involved in the treatment of the 56 patients who participated in this clinical trial. First, patients were injected with Toca 511, which is a replicating virus that only infects actively dividing tumor cells. Once inside the cancer cell, the virus delivered a gene for an enzyme, cytosine deaminase (CD). As the virus began to replicate and spread to other cancer cells, it programmed them to make CD. Next, patients received a pill, Toca FC, which is an inert compound. Once inside the cancer cell, CD converted Toca FC into the anticancer drug 5-fluorouracil, which killed the cancer cell. In addition to destroying the cancer cells, 5-fluorouracil killed certain immune suppressive myeloid cells, thus boosting the patient's immune system to recognize and attack the cancer cells. "The treatment we tested in this trial delivers local chemotherapy specifically to the brain tumor. Toca 511 and Toca FC work together to turn the brain tumor into a factory that produces an anticancer drug, while also activating the immune system through a combination of mechanisms, which together work to attack the cancer," Dr. Chen said.
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