New combination therapy fights brain cancer

Best Shot for GBM

New combination therapy fights brain cancer

By Ilene Schneider

A new vaccine has been developed that, along with high-dose chemotherapy, is intended to fight the tumor known as glioblastoma multiforme (GBM), which is the most malignant glial tumor. The findings were published in the journal of Clinical Cancer Research.

GBM spreads along neural pathways in the brain and gives the appearance of multiple lesions. Diagnosis is made using computed tomography, magnetic resonance imaging, positron emission tomography or magnetic resonance spectroscopy. Glioblastoma is the most common grade IV brain cancer. Glioblastoma may appear in any lobe of the brain, but it develops more commonly in the frontal and temporal lobes. The disease usually affects adults.

Patients present with gradually progressing motor weakness, headaches, nausea and vomiting. Cognitive impairment, sensory loss, aphasia, seizures and hemiparesis often follow. GBM is very aggressive, and currently available treatments can have serious side effects.There is no cure for GBM. Until now radiation has been used, with inconsistent results. Surgery is sometimes used to remove masses and lengthen survival time. The median survival rate for GBM patients has been under 15 months.

Glioblastoma can be hard to treat, because the tumors often contain so many different types of cells. While some cells may respond well to certain therapies, others may not be affected at all. For that reason, the treatment plan for glioblastoma may combine several approaches.

The new vaccine is specific for cytomegalo virus (CMV) antigen pp65, a protein produced by the CMV virus, and is used along with the anti-cancer drug temozolomide (TMZ). The CMV is attracted to GBM tumors and is found in 90 percent of them.

In a study, eleven patients with GBMs showed a median progression-free survival of 23 months a median overall survival of 41.1 months. Three patients were progression-free for more than 7 years.

“The clinical outcomes in GBM patients who received this combination were very striking,” said researcher Kristen Batich from Duke University in Durham, North Carolina.

“Our strategy was to capitalize on the immune deficiency caused by the temozolomide regimen," Batich said. "It seems counter-intuitive, but when the patient's lymphocytes are depleted, it's actually an optimal time to introduce the vaccine therapy. It basically gives the immune system marching orders to mount resources to attack the tumor."

TMZ causes lymphopenia, a large drop in the number of white blood cells that ingest foreign materials and are critical elements in the immune response. Thus, in conjunction with the vaccine it offers a chance to change and refocus the immune system.

“The dose-intensified temozolomide induces a strong state of lymphopenia," Batich continued. "With that comes an opportune moment to introduce an antigen-specific vaccine, which redirects the immune system to put all hands on deck and fight that target."

The dynamics of this altered immune response need to be studied further so they can be used to consistently create an even more successful therapy.  “We want to understand why some patients do better than others,” Batich concluded.