A new treatment for glioblastoma could enter clinical trials following the results of a new mouse study that looked at the effects of chemotherapy agent decitabine combined with T cell immunotherapy.
In the research appearing in Neuro-Oncology, Drs. Robert Prins and Linda Liau – both from the Jonsson Comprehensive Cancer Center at the University of California-Los Angeles – decitabine and genetically modified immune cells were tested as a combination in a continuation of previous research, which focused on decitabine against glioblastoma human cell cultures.
Their new work involved extracting and growing immune cells in culture, then reprogramming them with a gene known as New York Esophageal Squamous Cell Carcinoma, or NY-ESO-1.
The T cells were then injected back into tumor-bearing mice used as models of human brain cancer. This would produce an immune response to target the tumor.
Dr. Prins explains: “The lymphocytes will seek out and find the glioblastoma cells in the brain.” The associate professor in the departments of neurosurgery and molecular and medical pharmacology adds:
“They can cross different fiber tracts in the brain to reach tumor cells that have migrated away from the main tumor mass. These factors are important in the treatment of invasive tumors, such as glioblastoma.”
“While surgery to remove the main tumor mass can be done,” continues Dr. Prins, “it is not possible to then locate the tumor cells that get away and this ultimately leads to a nearly universal tumor regrowth.”
Glioblastoma cells do not naturally produce the NY-ESO-1 gene – which is where decitabine came in – used prior to injecting the NY-ESO-1-targeting T cells. The drug caused the tumor cells to express the NY-ESO-1 target.
The new method proved about 50% effective against glioblastoma in the early-stage study. The next stage for the researchers will be to verify their findings in other brain tumor models.
If results from that were also promising, the researchers would proceed with clinical trials in people.
“Brain cancer cells are very good at evading the host immune system, because they do not express specific targets that can be recognized by immune cells,” says Dr. Liau, professor and vice chair of neurosurgery.
“By treating glioblastoma cells with decitabine, we found that we can unmask targets on the tumor cell that can be recognized by killer T cells,” he adds. “Once these targets are uncovered, we can then administer T cells that are genetically programmed to attack tumor cells with the new targets.”