UCLA researchers develop new combination therapy to activate immune response against glioblastoma

UCLA researchers have developed a new breakthrough combination treatment that utilizes a vaccine to activate an immune response against advanced brain tumors. The therapy harnesses an antibody blockade to prevent the brain cancer from shielding itself from the patient's own immune cells so they can recognize the brain tumor and attack it.

The diagnosis of glioblastoma (GBM) is associated with an extremely poor prognosis in most people with the disease. It is estimated that median survival following traditional treatments, such as surgery, radiation and chemotherapy, is generally 14 to 18 months.

The new findings are published online in the journal JCI Insight.

The new three-year study led by Drs. Robert Prins, Linda Liau and Timothy Cloughesy, all UCLA Jonsson Comprehensive Cancer Center members, showed for the first time that a dendritic cell vaccine in combination with the antibody blockade of an immune cell surface receptor known as PD-1, generates a more effective immune response against GBM beyond the use of either treatment alone.

"These findings are the first that specifically outline the mechanism by which an effective immune response can be seen in tumors located in the brain," said Prins, an associate professor in the department of neurosurgery at UCLA. "We discovered that effective anti-tumor immunity to glioblastoma must have a significant infiltration of killer T cells and a blockade of the important checkpoint axes that make these killer T cells dysfunctional within the tumor."

Prins and his team added that the combination treatment is effective at reminding the immune system that the GBM is a foreign invader, essentially preventing the brain cancer from recurring or growing.

The administration of PD1/PD-L1 antibody blockade alone may not be successful in glioblastomas that do not have significant T-cell infiltration. Dendritic cell vaccination allows for infiltration of T cells into the brain tumors, while the PD-1 (mAb) antibody blockade removes the shield the tumor activates to hide from the immune system.

The methodology is different from previous research in metastatic melanoma and non-small cell lung cancer, as it shows that activation of an immune response using dendritic cell vaccination may be necessary in tumors that do not respond to PD-1/PD-L1 checkpoint inhibitors alone.

The next stage of research is to understand how the PD-1/PDL1 pathway signaling mechanism fits into other potential means of immune suppression currently being studied.