Combination Therapy May Eradicate Glioblastoma Cells

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Combination Therapy May Eradicate Glioblastoma Cells
Combination Therapy May Eradicate Glioblastoma Cells

Researchers from the University of California – Los Angeles may hold the key to the next treatment breakthrough for one of the most deadly types of brain cancers.

In a mouse study that served as a continuation of previous research on glioblastoma, researchers led by Robert Prins, PhD, studied the impact of a treatment combining the chemotherapy drug decitabine and genetically-modified immune cells.

The research involved engineered adoptive T cell transfer, in which immune cells are extracted and grown outside of the body, then reprogrammed with a gene for T cell receptor that targets New York esophageal squamous carcinoma (NY-ESO-1). Once the T cells are transformed, they are injected back into mice with glioblastoma tumors in order to produce an immune response that targets the specific brain cancer. Because glioblastoma cells do not naturally produce NY-ESO-1, the researchers had to administer decitabine prior to injecting the transformed T cells in order for the tumor cells to express the NY-ESO-1 target.

"The lymphocytes will seek out and find the glioblastoma cells in the brain," Prins said. "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, it is not possible to then locate the tumor cells that get away and this ultimately leads to a nearly universal tumor regrowth."

The researchers found that after injecting the mice with decitabine, expression of NY-ESO-1 was reliably and consistently induced specifically in glioma cells and not in normal brain tissue. Additionally, the upregulation of NY-ESO-1 by intracranial gliomas was associated with the migration of transferred NY-ESO-1 specific lymphocytes along white matter tracts to glioblastoma tumors. NY-ESO-1 adoptive T cell therapy also showed antitumor activity after decitabine treatment, with an approximate 50% cure rate observed.

"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," said researcher Linda M. Liau, MD, PhD. "Once these targets are uncovered, we can then administer T cells that are genetically programmed to attack tumor cells with the new targets."

The researchers now plan on testing the treatment against other brain cancer models.

Reference

  1. Everson RG et al. Neuro Oncol. 2015; doi:10.1093/neuonc/nov153. 
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