A combination of immune-stimulating and cell-killing drugs has showed encouraging early results in extending survival for gliomas, an aggressive brain cancer.
The researchers explored adenoviral gene therapy because gliomas have a dismal prognosis and limited response to chemotherapy and radiation. The Lancet Oncology research found the drug beneficial and safe.
“It’s exciting and a tour de force in translational medicine to move a novel therapy from bench to bedside in such a seamless manner,” said University of Michigan neurosurgeon professor Oren Sagher.
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The phase 1 trial focused on two genetic therapies for high-grade gliomas.
The first was HSV-1-TK and Valtrex, an antiviral used to treat chickenpox and cold sores.
HSV-1-TK turns Valtrex into a cytotoxic drug that kills cancer cells while they multiply. The second was Flt3L, which attracts brain-essential immune cells.
Early results from these therapies include improved survival. Six of the 18 research participants lived more than two years, three over three, and one—who is still alive—over five.
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This form of tumor has a bit over 14-month life expectancy with current treatment.
The medication was also safe for participants, therefore the maximal dose used in this experiment may be used in future trials.
Even though the adenoviral gene therapy vectors were only supposed to last a month, the HSV1-TK-expressing vector stayed active for 17 months.
This alters brain adenoviral gene therapy expectations and expands the window for employing HSV1-TK and Valtrex to prevent tumor recurrence.
Pedro Lowenstein, University of Michigan neurosurgery professor, says “this originated from a theoretical idea based on evolutionary hypotheses and was first tested in experimental models of the disease.”
Maria Castro, University of Michigan neurosurgery professor, said, “finally, after many years, we’re 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.”
Although further study is needed before this can be employed in the clinic, HSV1-TK’s long-term expression supports its usage to improve treatment. Based on this study, phase 1b/2 clinical trials can be designed.
The Lancet Oncology reported promising early findings in prolonging survival for aggressive brain cancer patients with gliomas. Since gliomas have a poor prognosis and limited response to chemotherapy and radiation, researchers examined adenoviral gene therapy. The medicine proved safe and effective in the research. The group focused on two genetic therapies for high-grade gliomas: HSV-1-TK and Valtrex. HSV-1-TK turns Valtrex into a cytotoxic chemical, killing cancer cells in progress. The brain receives critical immune cells from Flt3L, the second protein.
The study demonstrated that the adenoviral vector producing HSV1-TK was active for up to 17 months, changing expectations for brain adenoviral gene therapy and expanding the window of opportunity for utilizing HSV1-TK plus Valtrex to prevent tumor recurrence. HSV1-TK’s long-term expression facilitates therapeutic enhancement. Based on this study, phase 1b/2 clinical trials can be designed.