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A recent study from the University of Michigan Department of Neurosurgery and Rogel Cancer Centre demonstrates encouraging preliminary findings that a therapy combining cell-killing and immune-stimulating drugs is safe and effective in extending survival for patients with gliomas, a particularly aggressive type of brain cancer.
The findings of the study were published inThe Lancet Oncology. The study's lead authors, Rogel researchers Pedro Lowenstein, M.D., Ph.D., and Maria Castro, Ph.D., developed and investigated adenoviral-mediated gene treatments in their lab prior to this phase 1 first in person experiment. The team considered using the protein Flt3L to attract immune cells that are normally missing from the brain due to the poor prognosis of gliomas and their limited response to therapies like chemotherapy and radiation. To launch an immune response against cancer that is more powerful, these immune cells are necessary. Being able to move a novel therapy from bench to bedside in such a streamlined fashion is exciting, and represents a tour-de-force in translational medicine, said Oren Sagher, M.D., professor of neurosurgery at U-M and author of this study. The study focused on two types of genetic therapies in high-grade gliomas. The first was a combination of HSV-1-TK, a protein, and Valtrex, a drug used to treat viral infections like cold sores and chickenpox. HSV-1-TK turns Valtrex into a cytotoxic compound that kills actively dividing cancer cells. The second was Flt3L, a protein that recruits essential immune cells to the brain. When used in combination, these therapies showed exciting early results, including improved survival. Of the 18 patients enrolled in the trial, six survived more than two years, three survived more than three years, and one patient, who is still alive at the time of publication, survived up to five years. With current standard-of-care, the life expectancy for a tumor of this kind of just over 14 months. Further, the study found that this treatment wasnt toxic to the patients, suggesting that the highest dose used in this trial could be used in future trials. Though the adenoviral gene therapy vectors were supposed to be active for up to a month, work from three investigatorsMaria Luisa Varela, Ph.D., Mohammad Faisal Syed, Ph.D., and Molly West, Ph.D.discovered that activity from the adenoviral vector expressing the HSV1-TK was active for up to 17 months. This discovery changes expectations of adenoviral gene therapy in the brain and extends the potential time during which the combination HSV1-TK and Valtrex might be harnessed to combat tumor recurrence. This originated from a theoretical idea based on evolutionary hypotheses and was first tested in experimental models of the disease, said Lowenstein, Richard C. Schneider Collegiate Professor of Neurosurgery at U-M. Finally, after many years, were thrilled to report the results of testing this approach in human patients, obtaining results that will lead to better treatments for this group of brain tumor patients., said Maria Castro, Ph.D., Rogel member and professor of neurosurgery at U-M. (ANI)
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