The research goal is to activate the immune system to precisely target malignant brain glioma cells while simultaneously delivering radiation to the infiltrating tumor without harming adjacent normal brain cells.
The malignant cells of high grade glioblastomas that infiltrate healthy brain tissue are currently outside the reach of standard brain tumor therapies and are responsible for the inevitable recurrence of this cancer that kills within a year or two. The investigators will target tumor specific molecules that are found on the surface of more than 95 percent of glioblastoma cells but not on normal brain cells. These “biomarkers” provide the potential for activating immune cells to precisely target tumor cells while sparing adjacent normal tissue. They have developed a molecular scaffolding designed to recognize the biomarkers on tumor cells. Moreover, they can attach ultra short-range (nanometer) radioactivity to this molecule.
The researchers hypothesize, therefore, that they can precisely and simultaneously target glioblastoma cells with immunotherapy augmented by radiation while sparing nearby healthy brain cells. Furthermore, they hypothesize, the anti-tumor immune response that is elicited can protect against development of additional tumors. After producing the molecular scaffolding and attaching ultra short-range radioactivity to it, they will conduct laboratory experiments to see if the molecule attaches to glioblastoma cells—including those from tumors that had been surgically removed from patients and those from a glioblastoma cell line—but not to normal brain cells. Thereafter, they will test this experimental treatment on mice that have been implanted with cells from patients’ surgically removed tumors.
Significance: If successful, this experimental combination of immunotherapy and radiation treatment ultimately could be used in patients to eradicate infiltrating glioblastoma cells and prevent this deadly tumor’s recurrence while producing no collateral damage to normal brain tissues.