A new immunotherapy treatment created by Duke researchers holds promise for patients with aggressive brain tumors.
The researchers engineered a protein—bispecific T-cell engager or BiTE—that attacks the cancerous cells while sparing surrounding healthy tissue. The protein locates the tumor and attracts white blood cells called T-cells to attack the cancerous cells. The therapy was successful in six out of eight mice with brain tumors.
The scientists’ goal is to adapt the new treatment for humans with malignant brain tumors such as glioblastoma, said Dr. Darrell Bigner, director of the Preston Robert Tisch Brain Tumor Center. If the drug succeeds in clinical trials, it could change the current standard of care for these types of tumors.
“If [this treatment] is as successful in patients as it has been in the mice, it would be a completely new method of treating brain tumors and would potentially be much more effective than our current treatments and lack the toxicity of the current treatments,” said Bigner, who co-authored the paper on the BiTEs published in December in the Proceedings of the National Academy of Sciences.
Currently, a diagnosis of glioblastoma is followed by extensive surgery and toxic treatments such as radiation and chemotherapy, which can kill healthy cells inadvertently. These therapies mutate genes, making the cancer more difficult to treat in the future.
“When the patients recur they have thousands of new mutations in the genes and cancer genes,” Bigner said. “Even though you’ve got an additional few months of survival, you have created a very difficult type of recurrent tumor to treat because of these additional mutations.”
Even with current treatment, the median life expectancy after diagnosis is just 15 months, Bigner said.
Immunotherapy proposes an alternate approach to cancer treatment by utilizing the body’s own defense mechanisms to fight against the tumor.
“The protein acts like a little molecular lasso and attaches [the T-cell] to the cancer, allowing those T-cells in our bodies to discern between the cancer cell and a healthy cell,” said Bryan Choi, M.D.-Ph.D candidate at Duke and co-author of the study.
Because the therapy engages the natural immune system of the patient, it is much more specific in cell selection and much less toxic than current therapies, potentially reducing the painful side effects associated with radiation and chemotherapy.
The drug, administered intravenously, is also capable of crossing the blood-brain barrier, a historically challenging obstacle for larger molecules such as this coupled antibody. When given to the mice intravenously, the protein localized the tumor site within the brain, which is a crucial step in the therapy.
“The fact that it gets across the blood brain barrier is key because if you cannot deliver the drug there, then it’s never going to work,” said Dr. John Sampson, associate deputy director at the Preston Robert Tisch Brain Tumor Center and co-author of the study.
The intravenous administration is also much less laborious than current immunotherapy involving T-cells.
“In a lot of therapies that are going to target T-cells to tumor cells, you actually have to take the T-cells out of the body, grow them in a lab, and infect them with a virus,” said Sampson, who is also a professor of surgery, immunology, pathology, radiation oncology and neurosurgery.
The next step for this drug development involves altering the receptors to bind to human antibodies instead of mice antibodies. The long-term goal is to increase production of the drug to begin clinical trials on humans.
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